Academic Appointments


Administrative Appointments


  • Chairman, University panel on Radiation safety (2003 - 2010)

Professional Education


  • Licenciaat, KUL, Medical sciences (1978)
  • MD, Katholieke Universiteit Leuven, Medicine (1967)
  • PhD, UC Berkeley, Medical Physics (1972)

Current Research and Scholarly Interests


Radio-immunotherapy.
Medical Imaging Processing.
Quantification for diagnosis
Clinical validations

Clinical Trials


  • 90Y-IBRITUMOMAB Tiuxetan and AHCI With HD Chemotherapy and Autologous Transplantation for Relapsed or Resistant NHL Not Recruiting

    To test a new way to approach hematopoietic stem cell transplantation for Relapsed or Resistant Non-Hodgkin's Lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact BMT Referrals, (650) 723 - 0822.

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  • Assessing the Suitability of an Imaging Probe for Use in Clinical Cell and Gene Therapy Trials in Cancer and Rheumatoid Arthritis Not Recruiting

    The purpose of this study is to determine whether [18F]FHBG is suitable for use as an imaging probe in cancer or rheumatoid arthritis patients enrolled in cell or gene therapy trials. In this phase 1 study we will assess the safety and biodistribution of [18F]FHBG in patients.

    Stanford is currently not accepting patients for this trial. For more information, please contact Shahriar Shah Yaghoubi, Ph.D, 650-725-6070.

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  • Pilot Study to Determine Radioiodide Accumulation and Dosimetry in Breast Cancers Using 124I PET/CT Not Recruiting

    This is a pilot imaging study for women whose tumors express NIS [Na+I- symporter, sodium iodide symporter]. Eligibility is limited to the presence of strong (3+) and/or plasma membrane staining in > 20% of cells as determined by immunohistochemical methods. A total of 10 patients will be imaged with 124I PET/CT (serial scans over 24 hour period) to determine radioiodide uptake and distribution in tumor tissue. Thyroid iodide uptake and retention will be blocked beginning one week prior to 124I PET/CT scan with thyroid hormone (T3) and methimazole (impedes organification). Tumor, organ and whole body dosimetry will be calculated in each patient.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • Radioactive Iodide (131I) Treatment of 124I PET/CT Detected Breast Cancers Not Recruiting

    This is a treatment protocol designed to accompany the ongoing institutional 124I PET/CT pilot imaging study for patients with invasive breast cancer. Women whose tumors express NIS [Na+I- symporter, sodium iodide symporter] and demonstrate radioiodide uptake on 124I PET/CT scans will be eligible for 131I treatment if, (1) tumor dosimetry calculations yield a cumulative radiation dose of at least 30Gy in target tumor, (2) estimated cumulative thyroid irradiation is less than 500 cGy and, (3) the therapeutic dose of 131I is in the range of 25 to 100 mCi.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • Rituximab and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Non-Hodgkin's Lymphoma Not Recruiting

    RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with stage II, stage III, or stage IV diffuse large B-cell non-Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lauren Pernicka, (650) 721 - 6977.

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  • Rituximab, Combination Chemotherapy, and 90-Yttrium Ibritumomab Tiuxetan for Patients With Stage I or II Non-Hodgkin's Lymphoma Not Recruiting

    This phase II trial is studying how well giving rituximab together with combination chemotherapy and 90-Yttrium ibritumomab tiuxetan works in treating patients with stage I or stage II lymphoma. Drugs used in chemotherapy, such as prednisone, cyclophosphamide, doxorubicin, and vincristine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab and yttrium 90-Yttrium ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Combining a monoclonal antibody with combination chemotherapy and a radiolabeled monoclonal antibody may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office, (650) 498 - 7061.

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  • S0016 Combination Chemotherapy With Monoclonal Antibody Therapy in Newly Diagnosed Non-Hodgkin's Lymphoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and either kill them or deliver radioactive tumor-killing substances to them without harming normal cells. It is not yet known which monoclonal antibody plus combination chemotherapy regimen is more effective in treating non-Hodgkin's lymphoma. PURPOSE: This randomized phase III trial is comparing 2 different monoclonal antibodies given together with combination chemotherapy to see how well they work in treating patients with newly-diagnosed non-Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lauren Pernicka, (650) 721 - 6977.

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  • Scintigraphic Assessment of I- Transport in Metastatic Breast Cancer and Evaluation of I31I Ablative Therapy: (Part I) Radioiodide Imaging Study Not Recruiting

    The purpose of this study is to examine breast cancers that express the protein (NIS) that may be found in malignant breast tissues and to evaluate proteins found in blood and their relationship to NIS, to test whether iodide can be concentrated by breast cells to possibly treat some breast cancers with radioactive iodine, and to calculate the amount of radioactive iodine entering breast cancer cells, how long your cancer retains the agent as well as how much is taken up by other organs, particularly the thyroid gland.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • Study for Women With Platinum Resistant Ovarian Cancer Evaluating EC145 in Combination With Doxil® (PROCEED) Not Recruiting

    The purpose of this study is to compare progression-free survival (PFS) (based upon investigator assessment using RECIST v1.1) in participants with platinum-resistant ovarian cancer who receive combination therapy with EC145 and pegylated liposomal doxorubicin (EC145+PLD) with that in participants who receive PLD and placebo.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sharanya Ramasubramanian, 650-723-0622.

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  • Study of Bexxar <Tositumomab> Combined With External Beam Radiation Therapy Not Recruiting

    The purpose of the study is to assess the response rate of patients with relapsed or refractory low-grade or transformed low-grade, CD20-positive, B-cell non-Hodgkin's lymphoma to Iodine-131 (I-131) tositumomab (Bexxar) therapy plus local palliative radiation therapy (XRT).

    Stanford is currently not accepting patients for this trial. For more information, please contact Lucy Schoen, (650) 725 - 1718.

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2023-24 Courses


All Publications


  • Mucus plugging, air trapping, and bronchiectasis are important outcome measures in assessing progressive childhood cystic fibrosis lung disease. Pediatric pulmonology Robinson, T. E., Goris, M. L., Moss, R. B., Tian, L., Kan, P., Yilma, M., McCoy, K. S., Newman, B., de Jong, P. A., Long, F. R., Brody, A. S., Behrje, R., Yates, D. P., Cornfield, D. N. 2020

    Abstract

    OBJECTIVE: To determine which outcome measures could detect early progression of disease in school-age children with mild cystic fibrosis (CF) lung disease over a two-year time interval utilizing chest computed tomography (CT) scores, quantitative CT air trapping (QAT), and spirometric measurements.METHODS: Thirty-six school-age children with mild CF lung disease (median [interquartile range] age 12 [3.7] years; percent predicted forced expiratory volume in 1second (ppFEV1 ) 99 [12.5]) were evaluated by serial spirometer-controlled chest CT scans and spirometry at baseline, 3-month, 1- and 2-years.RESULTS: No significant changes were noted at 3-month for any variable except for decreased ppFEV1 . Mucus plugging score (MPS) and QATA1 and A2 increased at 1- and 2-years. The bronchiectasis score (BS), and total score (TS) were increased at 2-year. All variables tested with the exception of bronchial wall thickness score, parenchymal score (PS), and ppFEV1 , were consistent with longitudinal worsening of lung disease. Multivariate analysis revealed baseline PS, baseline TS, and 1-year changes in BS and air trapping score were predictive of 2-year changes in BS.CONCLUSIONS: MPS and QATA1-A2 were the most sensitive indicators of progressive childhood CF lung disease. The 1-year change in the bronchiectasis score had the most positive predictive power for 2-year change in bronchiectasis.

    View details for DOI 10.1002/ppul.24646

    View details for PubMedID 31962004

  • The strong but nonspecific relationship between F-18-FDG uptake in the lower-extremity veins and venous thromboembolism NUCLEAR MEDICINE COMMUNICATIONS Zhu, H. J., Hess, S., Rubello, D., Goris, M. L., Alavi, A. 2016; 37 (3): 322-328

    Abstract

    Venous thromboembolism (VTE) can present as deep vein thrombosis (DVT) and/or acute pulmonary embolism (PE). In fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT, 18F-FDG activity along the deep veins of the lower extremities (LE) is often observed and, unless it is associated with focal intense activity, is not considered abnormal. However, anecdotally it has been associated with the placement of an inferior vena cava filter. In this short paper we intend to investigate this association. We found 10 patients who were investigated in the vascular laboratory by means of either LE or upper-extremity duplex or a chest computed tomography with PE protocol, or who had undergone the placement of an inferior vena cava filter between 27 April 2010 and 7 January 2013 and who had also undergone one or more 18F-FDG-PET scan(s) that included the LE. Seventeen patients without venous 18F-FDG uptake were added as controls. 18F-FDG uptake visualized in the LE was scored as the number of positive LE veins and the extent of the radiotracer uptake. The time intervals between the VTE event and the 18F-FDG-PET scan(s) were recorded. The time intervals between the most remote and the closest 18F-FDG-PET before a VTE event averaged 79 ± 101 and 49 ± 82 days, respectively, and the closest and the most remote 18F-FDG-PET after the VTE event averaged 58 ± 50 and 122 ± 124 days. The extent of uptake in the LE veins averaged 7 ± 2 for the patients with an acute DVT on LE duplex and 5 ± 3 for those with negative or chronic DVT on LE duplex (P=nonsignificant). Two patients (n=3 and 10) were negative for VTE events and had an extent of 0. The number of positive events correlated slightly with the extent of venous uptake (r=0.69). The 17 control patients without venous uptake on 18F-FDG-PET had no history of VTE. There was an association between LE venous uptake of 18F-FDG and risk for VTE. The association was not related to the location of the VTE, nor to the timing of the VTE.

    View details for DOI 10.1097/MNM.0000000000000442

    View details for Web of Science ID 000373526600015

    View details for PubMedID 26671850

  • Fusion dual-tracer SPECT-based hepatic dosimetry predicts outcome after radioembolization for a wide range of tumour cell types EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Lam, M. G., Banerjee, A., Goris, M. L., Iagaru, A. H., Mittra, E. S., Louie, J. D., Sze, D. Y. 2015; 42 (8): 1192-1201

    Abstract

    Fusion dual-tracer SPECT imaging enables physiological rather than morphological voxel-based partitioning and dosimetry for (90)Y hepatic radioembolization (RE). We evaluated its prognostic value in a large heterogeneous cohort of patients with extensive hepatic malignancy.A total of 122 patients with primary or secondary liver malignancy (18 different cell types) underwent SPECT imaging after intraarterial injection of (99m)Tc macroaggregated albumin (TcMAA) as a simulation of subsequent (90)Y microsphere distribution, followed by administration of an excess of intravenous (99m)Tc-labelled sulphur colloid (TcSC) as a biomarker for functional liver, and a second SPECT scan. TcMAA distribution was used to estimate (90)Y radiation absorbed dose in tumour (D T) and in functional liver. Laboratory and clinical follow-up were recorded for 12 weeks after RE, and radiographic responses according to (m)RECIST were evaluated at 3 and 6 months. Dose-response relationships were determined for efficacy and toxicity.Patients were treated with a median of 1.73 GBq activity of resin microspheres (98 patients) or glass microspheres (24 patients), in a whole-liver approach (97 patients) or a lobar approach (25 patients). The objective response rate was 41 % at 3 months and 48 % at 6 months. Response was correlated with D T (P < 0.01). Median overall survival was 10.1 months (95 % confidence interval 7.4 - 12.8 months). Responders lived for 36.0 months compared to 8.7 months for nonresponders (P < 0.01). Stratified for tumour cell type, D T was independently associated with survival (P < 0.01). Absorbed dose in functional liver was correlated with toxicity grade change (P < 0.05) and RE-induced liver disease (P < 0.05).Fusion dual-tracer SPECT imaging offers a physiology-based functional imaging tool to predict efficacy and toxicity of RE. This technique can be refined to define dosing thresholds for specific tumour types and treatments, but appears generally predictive even in a heterogeneous cohort.

    View details for DOI 10.1007/s00259-015-3048-z

    View details for PubMedID 25916740

  • Prognostic Utility of Y-90 Radioembolization Dosimetry Based on Fusion Tc-99m-Macroaggregated Albumin-Tc-99m-Sulfur Colloid SPECT JOURNAL OF NUCLEAR MEDICINE Lam, M. G., Goris, M. L., Iagaru, A. H., Mittra, E. S., Louie, J. D., Sze, D. Y. 2013; 54 (12): 2055-2061

    Abstract

    Planning hepatic (90)Y radioembolization activity requires balancing toxicity with efficacy. We developed a dual-tracer SPECT fusion imaging protocol that merges data on radioactivity distribution with physiologic liver mapping.Twenty-five patients with colorectal carcinoma and bilobar liver metastases received whole-liver radioembolization with resin microspheres prescribed as per convention (mean administered activity, 1.69 GBq). As part of standard treatment planning, all patients underwent SPECT imaging after intraarterial injection of 37 MBq of (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) to simulate subsequent (90)Y distribution. Immediately afterward, patients received 185 MBq of labeled sulfur colloid ((99m)Tc-SC) intravenously as a biomarker for normal hepatic reticuloendothelial function and SPECT was repeated. The SPECT images were coregistered and fused. A region-based method was used to predict the (90)Y radiation absorbed dose to functional liver tissue (DFL) by calculation of (99m)Tc-MAA activity in regions with (99m)Tc-SC uptake. Similarly, the absorbed dose to tumor (DT) was predicted by calculation of (99m)Tc-MAA activity in voxels without (99m)Tc-SC uptake. Laboratory data and radiographic response were measured for 3 mo, and the survival of patients was recorded. SPECT-based DT and DFL were correlated with parameters of toxicity and efficacy.Toxicity, as measured by increase in serum liver enzymes, correlated significantly with SPECT-based calculation of DFL at all time points (P < 0.05) (mean DFL, 27.9 Gy). Broad biochemical toxicity (>50% increase in all liver enzymes) occurred at a DFL of 24.5 Gy and above. In addition, in uni- and multivariate analysis, SPECT-based calculation of DT (mean DT, 44.2 Gy) correlated with radiographic response (P < 0.001), decrease in serum carcinoembryonic antigen (P < 0.05), and overall survival (P < 0.01). The cutoff value of DT for prediction of 1-y survival was 55 Gy (area under the receiver-operating-characteristic curve = 0.86; P < 0.01). Patients who received a DT of more than 55 Gy had a median survival of 32.8 mo, compared with 7.2 mo in patients who received less (P < 0.05).Dual-tracer (99m)Tc-MAA-(99m)Tc-SC fusion SPECT offers a physiology-based imaging tool with significant prognostic power that may lead to improved personalized activity planning.

    View details for DOI 10.2967/jnumed.113.123257

    View details for Web of Science ID 000328013000006

  • Prognostic utility of 90Y radioembolization dosimetry based on fusion 99mTc-macroaggregated albumin-99mTc-sulfur colloid SPECT. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Lam, M. G., Goris, M. L., Iagaru, A. H., Mittra, E. S., Louie, J. D., Sze, D. Y. 2013; 54 (12): 2055-2061

    Abstract

    Planning hepatic (90)Y radioembolization activity requires balancing toxicity with efficacy. We developed a dual-tracer SPECT fusion imaging protocol that merges data on radioactivity distribution with physiologic liver mapping.Twenty-five patients with colorectal carcinoma and bilobar liver metastases received whole-liver radioembolization with resin microspheres prescribed as per convention (mean administered activity, 1.69 GBq). As part of standard treatment planning, all patients underwent SPECT imaging after intraarterial injection of 37 MBq of (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) to simulate subsequent (90)Y distribution. Immediately afterward, patients received 185 MBq of labeled sulfur colloid ((99m)Tc-SC) intravenously as a biomarker for normal hepatic reticuloendothelial function and SPECT was repeated. The SPECT images were coregistered and fused. A region-based method was used to predict the (90)Y radiation absorbed dose to functional liver tissue (DFL) by calculation of (99m)Tc-MAA activity in regions with (99m)Tc-SC uptake. Similarly, the absorbed dose to tumor (DT) was predicted by calculation of (99m)Tc-MAA activity in voxels without (99m)Tc-SC uptake. Laboratory data and radiographic response were measured for 3 mo, and the survival of patients was recorded. SPECT-based DT and DFL were correlated with parameters of toxicity and efficacy.Toxicity, as measured by increase in serum liver enzymes, correlated significantly with SPECT-based calculation of DFL at all time points (P < 0.05) (mean DFL, 27.9 Gy). Broad biochemical toxicity (>50% increase in all liver enzymes) occurred at a DFL of 24.5 Gy and above. In addition, in uni- and multivariate analysis, SPECT-based calculation of DT (mean DT, 44.2 Gy) correlated with radiographic response (P < 0.001), decrease in serum carcinoembryonic antigen (P < 0.05), and overall survival (P < 0.01). The cutoff value of DT for prediction of 1-y survival was 55 Gy (area under the receiver-operating-characteristic curve = 0.86; P < 0.01). Patients who received a DT of more than 55 Gy had a median survival of 32.8 mo, compared with 7.2 mo in patients who received less (P < 0.05).Dual-tracer (99m)Tc-MAA-(99m)Tc-SC fusion SPECT offers a physiology-based imaging tool with significant prognostic power that may lead to improved personalized activity planning.

    View details for DOI 10.2967/jnumed.113.123257

    View details for PubMedID 24144563

  • Safety of repeated yttrium-90 radioembolization. Cardiovascular and interventional radiology Lam, M. G., Louie, J. D., Iagaru, A. H., Goris, M. L., Sze, D. Y. 2013; 36 (5): 1320-1328

    Abstract

    PURPOSE: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. METHODS: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. RESULTS: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). CONCLUSION: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

    View details for DOI 10.1007/s00270-013-0547-9

    View details for PubMedID 23354961

  • An evaluation of the predictive value of mid-treatment F-18-FDG PET/CT scans in pediatric lymphomas and undefined criteria of abnormality in quantitative analysis HELLENIC JOURNAL OF NUCLEAR MEDICINE Zhu, H. J., Halkar, R., Alavi, A., Goris, M. L. 2013; 16 (3): 169-174

    Abstract

    Our purpose was to evaluate quantitative mid-treatment fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT scans in predicting the quantitative result of the end of treatment 18F-FDG PET/CT scan. With approval of Emory's Institutional Review Board, data were extracted from 273 existing 18F-FDG PET/CT scans of 143 pediatric patients performed for evaluation of lymphoma. The inclusion criteria were the availability of an initial staging scan (D0) and a mid-treatment scan after 1 to 3 cycles of chemotherapy (D1) and a post-treatment scan (D2). Absolute and relative changed of D1 compared to D0 were measured and their values in predicting D3 values were determined. Analysis was performed on a lesion basis (N=78) in 18 patients with an average of 4.3 lesions per patients. Results showed that the predictive value depended on the value selected as significant for the predictors (D1 SUV and D1 %SUV), and on the limit between negative and positive selected for the predicted value D2 SUV. If the maximum SUV<2.0 in D2 was the limit for negative, the negative predictive value if D1<4 was 0.84%. If positive was defined as D2>3.0, the positive predictive value of D1>4 was 100%. In that way outcome was predictable with absolute certainty in as many as 71% of the lesions with a single limit for D1 and D2. In conclusion, in this limited retrospective study the positive predictive value of the mid-treatment scan, was high for the post-treatment result for patient and lesion response seen on D2.

    View details for Web of Science ID 000327921200003

    View details for PubMedID 24137579

  • Brain uptake of Tc99m-HMPAO correlates with clinical response to the novel redox modulating agent EPI-743 in patients with mitochondrial disease MOLECULAR GENETICS AND METABOLISM Blankenberg, F. G., Kinsman, S. L., Cohen, B. H., Goris, M. L., Spicer, K. M., Perlman, S. L., Krane, E. J., Kheifets, V., Thoolen, M., Miller, G., Enns, G. M. 2012; 107 (4): 690-699

    Abstract

    While decreased ATP production and redox imbalance are central to mitochondrial disease pathogenesis, efforts to develop effective treatments have been hampered by the lack of imaging markers of oxidative stress. In this study we wished to determine if Tc99m-HMPAO, a SPECT imaging marker of cerebral blood flow and glutathione/protein thiol content, could be used to monitor the effect(s) of EPI-743, an oral redox modulating, para-benzoquinone based therapeutic for mitochondrial disease. We hypothesized that treatment changes in HMPAO uptake would be inversely proportional to changes in oxidative stress within the brain and directly correlate to clinical response to EPI-743 therapy. Twenty-two patients with mitochondrial disease were treated with EPI-743. Each underwent baseline and 3-month Tc99m-HMPAO SPECT scanning along with clinical/neurologic evaluations. Diseases treated were: Leigh syndrome (n=7), polymerase γ deficiency (n=5), MELAS (n=5), Friedreich ataxia (n=2), Kearns-Sayre syndrome, Pearson syndrome, and mtDNA depletion syndrome. Neuro-anatomic uptake analyses of HMPAO were performed with NeuroGam™ (Segami Corp.) statistical software and clinical response was assessed by the Newcastle Paediatric Mitochondrial Disease Scale or Newcastle Mitochondrial Disease Adult Scale depending on patient age. For all 22 patients there was a significant linear correlation between the change in cerebellar uptake of HMPAO and the improvement in Newcastle score (r=0.623, **p=0.00161). The MELAS subgroup showed a significant relationship of whole brain uptake (n=5, r=0.917, *p=0.028) to improvement in Newcastle score. We conclude that Tc99m-HMPAO SPECT scanning has promise as a general marker of the oxidative state of the brain and its response to redox modulating therapies. Further studies will be needed to confirm these findings in a more homogenous study population.

    View details for DOI 10.1016/j.ymgme.2012.09.023

    View details for Web of Science ID 000311816200010

    View details for PubMedID 23084792

  • Positron Emission Tomography of Cu-64-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL MOLECULAR IMAGING AND BIOLOGY Natarajan, A., Gowrishankar, G., Nielsen, C. H., Wang, S., Iagaru, A., Goris, M. L., Gambhir, S. S. 2012; 14 (5): 608-616

    Abstract

    This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation.(64)Cu was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed. The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n = 3) that received 7.4 MBq/dose, (b) with pre-dose (CD20TM, n = 6) received 2 mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4 MBq/dose, and (c) without pre-dose (CD20TM, n = 6) PETRIT alone received 7.4 MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs.PETRIT was obtained with a specific activity of 545 ± 38.91 MBq/nmole, radiochemical purity >95%, and immunoreactivity >75%. At 24 h, spleenic uptake of PETRIT%ID/g (mean ± STD) with and without pre-dose was 1.76 ± 0.43% and 16.5 ± 0.45%, respectively (P value = 0.01). Liver uptake with and without pre-dose was 0.41 ± 0.51% and 0.52 ± 0.17% (P value = 0.86), respectively. The human equivalents of highest dose organs with and without pre-dose are osteogenic cells at 30.8 ± 0.4 μSv/MBq and the spleen at 99 ± 4 μSv/MBq, respectively.PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non-Hodgkins lymphoma patients.

    View details for DOI 10.1007/s11307-011-0537-8

    View details for Web of Science ID 000308819300011

    View details for PubMedID 22231277

  • Targeted Systemic Radiotherapy with scVEGF/Lu-177 Leads to Sustained Disruption of the Tumor Vasculature and Intratumoral Apoptosis JOURNAL OF NUCLEAR MEDICINE Blankenberg, F. G., Levashova, Z., Goris, M. G., Hamby, C. V., Backer, M. V., Backer, J. M. 2011; 52 (10): 1630-1637

    Abstract

    Tumor vessels abundantly express receptors for vascular endothelial growth factor (VEGF), despite treatment with conventional or antiangiogenic drugs. We wished to determine whether the high levels of VEGF receptor (VEGFR) within the tumor vasculature could be leveraged for intracellular delivery of therapeutically significant doses of scVEGF/(177)Lu, a novel radiopharmaceutical based on a recombinant single-chain (sc) derivative of VEGF, in orthotopic breast cancer models.scVEGF-PEG (polyethylene gycol)-DOTA conjugates containing 2.0-, 3.4-, or 5.0-kDa PEG linkers site-specifically conjugated to a cysteine-containing tag (Cys-tag) in scVEGF were radiolabeled with (177)Lu (scVEGF/(177)Lu) for in vivo studies. Human MDA231luc and mouse 4T1luc cell lines were injected orthotopically to establish breast carcinoma tumors in immunodeficient and immunocompetent hosts, respectively. The effects of scVEGF/(177)Lu were defined by analysis of changes in tumor growth and immunohistochemical staining for the endothelial markers CD31 and VEGFR-2 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining for intratumoral apoptosis.Biodistribution assays and dosimetric calculations established that scVEGF/(177)Lu with a 3.4-kDa PEG linker delivered the highest dose of radiation to tumors (69.9 cGy/MBq/g of tissue) and the lowest dose to the kidneys (33.3 cGy/MBq/organ). Total doses below 40 MBq/mouse of scVEGF/(177)Lu did not affect renal function, and 3 divided doses of 6.3 MBq/mouse or a bolus dose of 18.9 MBq/mouse induced only transient lymphopenia and weight loss (<10% baseline weight). In mice with orthotopic mammary breast carcinoma, intravenous injections of well-tolerated bolus and fractionated doses of scVEGF/(177)Lu in the range from 6.3 to 18.9 MBq/mouse (25-76 MBq/m(2)) resulted in dose-dependent tumor growth inhibition. Immunohistochemical analysis of tumors at 4-5 wk after single injections of scVEGF/(177)Lu indicated dose-dependent regression of tumor vasculature and widespread intratumoral apoptosis. A single dose of 7.4 MBq/mouse of scVEGF/(177)Lu given before a course of bevacizumab or sunitinib treatment enhanced the antiangiogenic effects of both drugs.Selective targeting of VEGFR in tumor vasculature with well-tolerated doses of scVEGF/(177)Lu is effective in orthotopic breast cancer models. As high levels of VEGFR expression in the tumor vasculature are a common feature in a variety of cancers, targeting tumor angiogenesis with scVEGF/(177)Lu warrants further exploration.

    View details for DOI 10.2967/jnumed.111.091629

    View details for PubMedID 21890879

  • Pilot Pharmacokinetic and Dosimetric Studies of F-18-FPPRGD2: A PET Radiopharmaceutical Agent for Imaging alpha(v)beta(3) Integrin Levels RADIOLOGY Mittra, E. S., Goris, M. L., Iagaru, A. H., Kardan, A., Burton, L., Berganos, R., Chang, E., Liu, S., Shen, B., Chin, F. T., Chen, X., Gambhir, S. S. 2011; 260 (1): 182-191

    Abstract

    To assess the safety, biodistribution, and dosimetric properties of the positron emission tomography (PET) radiopharmaceutical agent fluorine 18 ((18)F) FPPRGD2 (2-fluoropropionyl labeled PEGylated dimeric RGD peptide [PEG3-E{c(RGDyk)}2]), which is based on the dimeric arginine-glycine-aspartic acid (RGD) peptide sequence and targets α(v)β(3) integrin, in the first volunteers imaged with this tracer.The protocol was approved by the institutional review board, and written informed consent was obtained from all participants. Five healthy volunteers underwent whole-body combined PET-computed tomography 0.5, 1.0, 2.0, and 3.0 hours after tracer injection (mean dose, 9.5 mCi ± 3.4 [standard deviation] [351.5 MBq ± 125.8]; mean specific radioactivity, 1200 mCi/mmol ± 714 [44.4 GBq/mmol ± 26.4]). During this time, standard vital signs, electrocardiographic (ECG) readings, and blood sample values (for chemistry, hematologic, and liver function tests) were checked at regular intervals and 1 and 7 days after the injection. These data were used to evaluate tracer biodistribution and dosimetric properties, time-activity curves, and the stability of laboratory values. Significant changes in vital signs and laboratory values were evaluated by using a combination of population-averaged generalized estimating equation regression and exact paired Wilcoxon tests.The administration of (18)F-FPPRGD2 was well tolerated, with no marked effects on vital signs, ECG readings, or laboratory values. The tracer showed the same pattern of biodistribution in all volunteers: primary clearance through the kidneys (0.360 rem/mCi ± 0.185 [0.098 mSv/MBq ± 0.050]) and bladder (0.862 rem/mCi ± 0.436 [0.233 mSv/MBq ± 0.118], voiding model) and uptake in the spleen (0.250 rem/mCi ± 0.168 [0.068 mSv/MBq ± 0.046]) and large intestine (0.529 rem/mCi ± 0.236 [0.143 mSv/MBq ± 0.064]). The mean effective dose of (18)F-FPPRGD2 was 0.1462 rem/mCi ± 0.0669 (0.0396 mSv/MBq ± 0.0181). With an injected dose of 10 mCi (370 MBq) and a 1-hour voiding interval, a patient would be exposed to an effective radiation dose of 1.5 rem (15 mSv). Above the diaphragm, there was minimal uptake in the brain ventricles, salivary glands, and thyroid gland. Time-activity curves showed rapid clearance from the vasculature, with a mean 26% ± 17 of the tracer remaining in the circulation at 30 minutes and most of the activity occurring in the plasma relative to cells (mean whole blood-plasma ratio, 0.799 ± 0.096).(18)F-FPPRGD2 has desirable pharmacokinetic and biodistribution properties. The primary application is likely to be PET evaluation of oncologic patients-especially those with brain, breast, or lung cancer. Specific indications may include tumor staging, identifying patients who would benefit from antiangiogenesis therapy, and separating treatment responders from nonresponders early.

    View details for DOI 10.1148/radiol.11101139

    View details for Web of Science ID 000291932300021

    View details for PubMedID 21502381

    View details for PubMedCentralID PMC3121013

  • I-131-Tositumomab (BexxarA (R)) vs. Y-90-Ibritumomab (ZevalinA (R)) Therapy of Low-Grade Refractory/Relapsed Non-Hodgkin Lymphoma MOLECULAR IMAGING AND BIOLOGY Iagaru, A., Mittra, E. S., Ganjoo, K., Knox, S. J., Goris, M. L. 2010; 12 (2): 198-203

    Abstract

    The American Cancer Society estimated 66,120 new cases of non-Hodgkin lymphoma (NHL) in the USA in 2008. Radioimmunotherapy has been shown in clinical trials to be an effective treatment for refractory/relapsed NHL. The available agents are Bexxar, a (131)I radiolabeled murine monoclonal antibody, and Zevalin, a (90)Y radiolabeled murine antibody. Both target CD20 receptors present on the surface of lymphocytes. We present our clinical experience with Bexxar and Zevalin in the management of low-grade refractory or relapsed NHL.This is a retrospective study (Jan 2000-Jul 2006) of 67 patients with NHL, who were treated with Bexxar (31 patients, group A) or Zevalin (36 patients, group B) for refractory/relapsed disease. Group A included 16 men and 15 women, 35-81 years old (average, 59.3 +/- 13.4). Group B included 27 men and nine women, 36-85 years old (average, 55.4 +/- 13.8). Therapeutic doses ranged 40-138 mCi (average, 78.1 +/- 28.2) for Bexxar and 17-34 mCi (average, 28.8 +/- 4.37) for Zevalin.Objective responses were induced in 22 of the 31 patients (70.9%) in group A and 28 of the 36 patients (77.8%) in group B. Complete response was noted in 11 patients (35.5%), partial response in seven patients (22.6%), and mixed response in four patients (12.9%) in group A. There were five patients (16.1%) with stable disease and four patients (12.9%) with disease progression in the same group. Complete response was noted in 15 patients (41.7%), partial response in nine patients (25%), and mixed response in four patients (11.1%) in group B. There were four patients (11.1%) with stable disease and another four patients (11.1%) with disease progression in the same group. The average decreases at posttherapy nadir were 36.9% +/- 0.33 (group A) and 52.6% +/- 0.32 (group B) for platelets, 27.8% +/- 0.27 (group A) and 34.2% +/- 0.38 (group B) for leukocytes, and 4.9% +/- 0.15 (group A) and 7.6% +/- 0.11 (group B) for hemoglobin. Grades 3 and 4 hematological toxicity occurred in 14 patients (45.2%) treated with Bexxar and 22 patients (61.1%) treated with Zevalin, but was reversible.Our study suggests that clinical practice of Bexxar and Zevalin radioimmunotherapy is an effective and safe adjunctive treatment for patients with NHL refractory/relapsed to conventional treatment. However, due to the small number of subjects, it was not possible to determine whether differences in the outcomes or toxicities from the two agents were statistically significant.

    View details for DOI 10.1007/s11307-009-0245-9

    View details for Web of Science ID 000275974900010

    View details for PubMedID 19543946

  • Incorporating Cone-beam CT into the Treatment Planning for Yttrium-90 Radioembolization JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Louie, J. D., Kothary, N., Kuo, W. T., Hwang, G. L., Hofmann, L. V., Goris, M. L., Iagaru, A. H., Sze, D. Y. 2009; 20 (5): 606-613

    Abstract

    To prepare for yttrium-90 ((90)Y) microsphere radioembolization therapy, digital subtraction angiography (DSA) and technetium- 99m-labeled macroaggregated albumin ((99m)Tc MAA) scintigraphy are used for treatment planning and detection of potential nontarget embolization. The present study was performed to determine if cone-beam computed tomography (CBCT) affects treatment planning as an adjunct to these conventional imaging modalities.From March 2007 to August 2008, 42 consecutive patients (21 men, 21 women; mean age, 59 years; range, 21-75 y) who underwent radioembolization were evaluated by CBCT in addition to DSA and (99m)Tc MAA scintigraphy during treatment planning, and their records were retrospectively reviewed. The contrast-enhanced territories shown by CBCT with selective intraarterial contrast agent administration were used to predict intrahepatic and possible extrahepatic distribution of microspheres.In 22 of 42 cases (52%), extrahepatic enhancement or incomplete tumor perfusion seen on CBCT affected the treatment plan. In 14 patients (33%), the findings were evident exclusively on CBCT and not detected by DSA. When comparing CBCT versus (99m)Tc MAA scintigraphy, CBCT showed eight cases of extrahepatic enhancement (19%) that were not evident on (99m)Tc MAA imaging. CBCT findings directed the additional embolization of vessels or repositioning of the catheter for better contrast agent and microsphere distribution. One case of gastric ulcer from nontarget embolization caused by reader error was observed.CBCT can provide additional information about tumor and tissue perfusion not currently detectable by DSA or (99m)Tc MAA imaging, which should optimize (90)Y microsphere delivery and reduce nontarget embolization.

    View details for DOI 10.1016/j.jvir.2009.01.021

    View details for PubMedID 19345589

  • Novel Strategy for a Cocktail F-18-Fluoride and F-18-FDG PET/CT Scan for Evaluation of Malignancy: Results of the Pilot-Phase Study JOURNAL OF NUCLEAR MEDICINE Iagaru, A., Mittra, E., Yaghoubi, S. S., Dick, D. W., Quon, A., Goris, M. L., Gambhir, S. S. 2009; 50 (4): 501-505

    Abstract

    (18)F-FDG PET/CT is used for detecting cancer and monitoring cancer response to therapy. However, because of the variable rates of glucose metabolism, not all cancers are identified reliably. Sodium (18)F was previously used for bone imaging and can be used as a PET/CT skeletal tracer. The combined administration of (18)F and (18)F-FDG in a single PET/CT study for cancer detection has not been reported to date.This is a prospective pilot study (November 2007-November 2008) of 14 patients with proven malignancy (6 sarcoma, 3 prostate cancer, 2 breast cancer, 1 colon cancer, 1 lung cancer, and 1 malignant paraganglioma) who underwent separate (18)F PET/CT and (18)F-FDG PET/CT and combined (18)F/(18)F-FDG PET/CT scans for the evaluation of malignancy (a total of 3 scans each). There were 11 men and 3 women (age range, 19-75 y; average, 50.4 y).Interpretation of the combined (18)F/(18)F-FDG PET/CT scans compared favorably with that of the (18)F-FDG PET/CT (no lesions missed) and the (18)F PET/CT scans (only 1 skull lesion seen on an (18)F PET/CT scan was missed on the corresponding combined scan). Through image processing, the combined (18)F/(18)F-FDG scan yielded results for bone radiotracer uptake comparable to those of the (18)F PET/CT scan performed separately.Our pilot-phase prospective trial demonstrates that the combined (18)F/(18)F-FDG administration followed by a single PET/CT scan is feasible for cancer detection. This combined method opens the possibility for improved patient care and reduction in health care costs.

    View details for DOI 10.2967/jnumed.108.058339

    View details for Web of Science ID 000272487200003

    View details for PubMedID 19289439

  • Endogenous NIS Expression in Triple-Negative Breast Cancers ANNALS OF SURGICAL ONCOLOGY Renier, C., Yao, C., Goris, M., Ghosh, M., Katznelson, L., Nowles, K., Gambhir, S. S., Wapnir, I. 2009; 16 (4): 962-968

    Abstract

    The sodium iodide symporter (NIS) mediates iodide transport into cells and has been identified in approximately 70% of breast cancers. Functional NIS expression raises the possibility of using (131)I for therapeutic targeting of tumor cells. Treatment of triple-negative breast cancers [estrogen/progesterone receptor-negative and HER2-negative (ER-/PR-/HER2-)] is primarily limited to chemotherapy. Our aim was to characterize NIS expression in this subset of tumors.Archival tissue sections from 23 women with triple-negative breast cancer were analyzed for NIS expression using immunohistochemical methods and an anti-human NIS antibody. Tumors were evaluated for the presence of plasma membrane immunoreactivity. One patient with a NIS-expressing positive tumor underwent (123)I scintigraphic imaging with dosimetric analysis.Fifteen cases (65.2%) demonstrated NIS-positivity with 11 tumors (47.8%) exhibiting strong expression. Plasma membrane immunoreactivity was observed in four breast cancers and was equivocal in another four tumors. Tumor-specific radioiodide uptake was demonstrated by (123)I scintigraphy in a patient with a large primary breast cancer unresponsive to neoadjuvant therapy. The tumor concentrated 2.05, 1.53, and 1.96 times more isotope than normal breast tissue at 1, 5, and 21 h. The relative increased uptake is consistent with positive NIS expression in the tumor on definitive surgery; however, the cumulative concentration in the tumor was not sufficient to achieve a therapeutic effect, had the isotope been (131)I.NIS is strongly expressed in a significant proportion of triple-negative breast cancer cells, suggesting a potential role for NIS-directed (131)I-radioablative strategies in this patient population.

    View details for DOI 10.1245/s10434-008-0280-9

    View details for PubMedID 19184238

  • Quantitative Analysis of Longitudinal Response to Aerosolized Granulocyte-Macrophage Colony-Stimulating Factor in Two Adolescents With Autoimmune Pulmonary Alveolar Proteinosis CHEST Robinson, T. E., Trapnell, B. C., Goris, M. L., Quittell, L. M., Cornfield, D. N. 2009; 135 (3): 842-848

    Abstract

    Autoimmune pulmonary alveolar proteinosis (APAP) is characterized by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in blood and tissues, resulting in alveolar surfactant protein accumulation. Patients with APAP present with ground-glass opacities (GGOs) and interlobular septal thickening on thin-slice chest CT scans. Aerosolized GM-CSF therapy (aeroGM-SCF) has qualitatively improved the clinical condition of patients with APAP. This report details quantitative chest CT responses to aeroGM-CSF.Two adolescent patients (aged 16 and 19 years) with APAP were treated with aeroGM-CSF. Clinical parameters, including pulmonary function tests and chest CT scans, were obtained before and after aeroGM-CSF therapy. To evaluate the effect of the therapy, serial chest CT scans were analyzed using a novel approach permitting quantitative assessment of improvement in GGOs, lung weight, and gas volume.In association with GM-CSF treatment, nutritional status and pulmonary function improved. Quantitative analysis of the CT scans demonstrated reduction in GGOs and lung weight, concomitant with an increase in airspace volume and lung inflation. The findings were consistent with a qualitative reduction in GGOs on chest CT imaging.Quantitative analysis of CT holds promise as a sensitive diagnostic tool permitting longitudinal and objective analysis of the therapeutic response to aeroGM-CSF in patients with APAP.

    View details for DOI 10.1378/chest.08-1317

    View details for Web of Science ID 000264310500034

    View details for PubMedID 19265094

  • Sampling density for the quantitative evaluation of air trapping PEDIATRIC RADIOLOGY Goris, M. L., Robinson, T. E. 2009; 39 (3): 221-225

    Abstract

    Concerns have been expressed recently about the radiation burden on patient populations, especially children, undergoing serial radiological testing. To reduce the dose one can change the CT acquisition settings or decrease the sampling density.In this study we determined the minimum desirable sampling density to ascertain the degree of air trapping in children with cystic fibrosis.Ten children with cystic fibrosis in stable condition underwent a volumetric spiral CT scan. The degree of air trapping was determined by an automated algorithm for all slices in the volume, and then for 1/2, 1/4, to 1/128 of all slices, or a sampling density ranging from 100% to 1% of the total volume. The variation around the true value derived from 100% sampling was determined for all other sampling densities.The precision of the measurement remained stable down to a 10% sampling density, but decreased markedly below 3.4%.For a disease marker with the regional variability of air trapping in cystic fibrosis, regardless of observer variability, a sampling density below 10% and even more so, below 3.4%, apparently decreases the precision of the evaluation.

    View details for DOI 10.1007/s00247-008-1076-6

    View details for Web of Science ID 000263097600005

    View details for PubMedID 19096836

  • Y-90-Ibritumomab Therapy in Refractory Non-Hodgkin's Lymphoma: Observations from In-111-Ibritumomab Pretreatment Imaging JOURNAL OF NUCLEAR MEDICINE Iagaru, A., Gambhir, S. S., Goris, M. L. 2008; 49 (11): 1809-1812

    Abstract

    Radioimmunotherapy is an effective treatment for non-Hodgkin's lymphoma (NHL). 90Y-ibritumomab is an antibody targeting CD20 receptors on the surface of lymphocytes. We present observations from our clinical experience with 90Y-ibritumomab in the management of NHL.This was a retrospective study of 28 NHL patients treated with 90Y-ibritumomab. There were 21 men and 7 women, 36-85 y old. A diagnostic dose of 111In-ibritumomab was administered on day 0, and imaging followed immediately and at 24, 48, and 72 h. The doses of 90Y-ibritumomab ranged from 629 to 1,258 MBq (17-34 mCi). Outcomes were compared with the findings of the 111In-ibritumomab scans.90Y-ibritumomab induced objective responses in 22 of 28 patients. A complete response was noted in 9 patients, a partial response in 9 patients, and a mixed response in 4 patients. Three patients had stable disease, and 3 patients had disease progression. 111In-ibritumomab findings were positive in 19 patients and negative in 9 patients. A complete response was noted in 2 of 19 patients with positive findings and 7 of 9 with negative findings. A partial response was seen in 7 of 19 patients with positive findings and 1 of 9 with negative findings. Disease progression was observed in 3 of 19 patients with positive findings and 0 of 9 with negative findings. The remaining patients had a mixed response or no changes.A higher rate of complete response after 90Y-ibritumomab treatment was seen in patients with negative 111In-ibritumomab findings, whereas a higher rate of disease progression despite therapy was noted in patients with positive 111In-ibritumomab findings. This observation suggests that patients with bulky disease may require more aggressive management.

    View details for DOI 10.2967/jnumed.108.052928

    View details for Web of Science ID 000260846600019

    View details for PubMedID 18927323

  • F-18-FDG-PET/CT evaluation of response to treatment in lymphoma: when is the optimal time for the first re-evaluation scan? HELLENIC JOURNAL OF NUCLEAR MEDICINE Iagaru, A., Wang, Y., Mari, C., Quon, A., Goris, M. L., Horning, S., Gambhir, S. S. 2008; 11 (3): 153-156

    Abstract

    Assessing the response to treatment as soon after treatment initiation is one of the key reasons for imaging lymphoma patients. The optimal time after initiating treatment for assessing response to treatment has yet to be determined. Therefore, we were prompted to review our experience with serial (18)F-FDG PET/CT in patients undergoing treatment for Hodgkin's disease (HD) and non Hodgkin's lymphoma (NHL). This is a retrospective study (Feb 2003 - Oct 2004) of 20 patients, 11 men and 9 women, with age range of 7-75 years with diagnosis of HD (10) and NHL (10), who had PET/CT at our institution prior, during and at the completion of therapy. Restaging PET/CT was done after 2 cycles of chemotherapy in 10 patients (group A) and after 4 cycles of chemotherapy in 10 pts (group B). A total of 60 scans were reviewed. The DeltaSUV from baseline to first PET/CT was on average 67.6% in group A and 75.1% in group B. This had no statistical significance (P value: 0.31). The DeltaSUV from baseline to post-therapy PET/CT was on average 72.9% in group A and 79.8% in group B. This difference also had no statistical significance (P value: 0.24). The correlation coefficient was 0.98 in group A and 0.80 in group B. Results of PET/CT after 2 cycles of chemotherapy did not statistically differ from the results of PET/CT after 4 cycles of chemotherapy. These results need to be confirmed in larger, prospective, randomized trials.

    View details for Web of Science ID 000262093600003

    View details for PubMedID 19081857

  • Rhabdomyosarcoma diffusely metastatic to the bone marrow: suspicious findings on Tc-99m-MDP bone scintigraphy confirmed by F-18-18 FDG PET/CT and bone marrow biopsy EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Iagaru, A., Goris, M. L. 2008; 35 (9): 1746-1746

    View details for DOI 10.1007/s00259-008-0864-4

    View details for Web of Science ID 000258673800026

    View details for PubMedID 18648808

  • Perspectives of molecular imaging and radioimmunotherapy in lymphoma RADIOLOGIC CLINICS OF NORTH AMERICA Iagaru, A., Goris, M. L., Gambhir, S. S. 2008; 46 (2): 243-252

    Abstract

    Successful treatment of Hodgkin lymphomas and non-Hodgkin lymphomas depends on accurate staging and prognostic estimations, as well as evaluation of response to therapy as early after initiation as possible. We focus on several aspects of molecular imaging and therapy that affect the management of patients who have lymphoma. First, we review prior use of gallium-67 citrate for evaluation of lymphoma patients, mainly from a historical perspective, since it was the mainstream lymphoma functional imaging tracer for decades. Next, we review current clinical uses of 18F Fluoro-2-Deoxyglucose (18F FDG) PET and PET/CT for evaluation of lymphoma patients and use of radioimmunotherapy in lymphoma. Finally, we discuss advances in molecular imaging that may herald the next generation of PET radiotracers after 18F FDG.

    View details for DOI 10.1016/j.rcl.2008.03.007

    View details for Web of Science ID 000258543500006

    View details for PubMedID 18619379

  • Monitoring the protective effects of minocycline treatment with radiolabeled annexin v in an experimental model of focal cerebral ischemia JOURNAL OF NUCLEAR MEDICINE Tang, M. N., Wang, Q., Koikel, M. A., Cheng, D., Goris, M. L., Blankenberg, F. G., Yenari, M. A. 2007; 48 (11): 1822-1828

    Abstract

    Minocycline is an antibiotic now recognized to have antiapoptotic and antiinflammatory properties. Because of these properties, minocycline may be of benefit in reducing neuronal apoptosis from ischemia and subsequent postischemic inflammation if administered soon after a stroke. We now explore the feasibility of using (99m)Tc-annexin V, an in vivo marker of apoptosis, with SPECT to monitor the antiapoptotic effects of minocycline therapy.CB6/F1 adult male mice underwent unilateral distal middle cerebral artery occlusion (dMCA) occlusion and were imaged and sacrificed at 1, 3, 7, or 30 d after injury. Animals were given minocycline (or vehicle) 30 min and 12 h after dMCA occlusion and then given 22.5 mg/kg twice daily for up to 7 d. Before imaging, behavioral tests were performed to evaluate the neurologic function. After imaging, brains were collected for histology and assessed for the degree of apoptosis and microglial activation.(99m)Tc-Annexin V uptake in injured hemispheres was significantly decreased 2- to 3-fold by minocycline at all time points. Minocyline reduced infarct size as seen histologically and improved behavioral indices as late as 30 d. Infarct volume as seen histologically correlated with radiolabeled annexin V uptake seen by SPECT. In situ fluorescent microscopy demonstrated that annexin V bound primarily to neurons at 1 and 3 d, with a shift toward microglia by 7 and 30 d.We found that minocycline significantly reduces neuronal apoptosis and infarct size and improves neurologic outcome in mice after acute focal cortical ischemia.

    View details for DOI 10.2967/jnumed.107.041335

    View details for Web of Science ID 000252894900019

    View details for PubMedID 17942809

  • A critical discussion of computer analysis in medical imaging. Proceedings of the American Thoracic Society Goris, M. L., Zhu, H. J., Robinson, T. E. 2007; 4 (4): 347-349

    Abstract

    Medical imaging has increasingly provided surrogate endpoints in therapeutic trials. This use assumes that the interpretation of the images can be unbiased and reproducible and that the image attributes included in the interpretation are relevant to the mechanism of the trial. The principal motivation for computer analysis is to evaluate an attribute of the image as a metric in an algorithmic manner, independent of observer bias or variability. The metric is expected to reflect change in rough proportion with at least one aspect of the degree of disease or the effectiveness of the therapeutic intervention. If either condition is satisfied, the measure is quantitative. Visual interpretation explicitly or implicitly tends to be based on multiple image attributes. Explicit combination of multiple attributes yields composite scores. To evaluate the risk or probability of disease, they are useful. But the components of the scores can be combined only if they are mathematically isomorphic. For the evaluation of interventions, they are less useful because the effect on one component may be obscured by the lack of effect on other components. This article reviews quantification of air trapping in cystic fibrosis and quantification in general. Validation of any computer analysis can rely on agreement with visual interpreters (on average), they can be derived from first principles, or by agreement with an alternative method that measures the pathophysiological mechanism directly (xenon washout for air trapping). However, in the context of trials, the validation may come from a superior ability to detect objective change and to discriminate between affected and unaffected individuals.

    View details for PubMedID 17652499

  • Evaluation of herpes simplex virus 1 thymidine kinase-mediated trapping of I-131 FIAU and prodrug activation of ganciclovir as a synergistic cancer radio/chemotherapy MOLECULAR IMAGING AND BIOLOGY Schipper, M. L., Goris, M. L., Gambhir, S. S. 2007; 9 (3): 110-116

    Abstract

    Evaluation of selective killing of Herpes Simplex Virus 1 thymidine kinase (HSV1-tk) expressing tumors by radiolabeled (131)I-fialuridine (FIAU), and of synergy between (131)I-FIAU and Ganciclovir (GCV).HSV1-tk-expressing cell lines and parental cell lines were exposed to (131)I-FIAU alone, GCV alone, or combinations. Activity and concentration were varied widely, concurrent and sequential administrations tested, and dose rate effects were studied.HSV1-tk-expressing cells accumulated up to 15.7-fold more (131)I-FIAU, were growth inhibited by 2 muCi/ml, or 5 muCi/ml (131)I-FIAU, and were inhibited by two log orders lower concentrations of GCV than parental cells. However, no synergy or additive effect was observed. Dose rate variations, or sequential treatment, did not alter outcome.Radioisotope therapy of HSV1-tk-expressing tumor cells with (131)I-FIAU is reported for the first time. Lack of synergy between (131)I-FIAU and GCV does not warrant further investigation of combination treatment with the two agents.

    View details for DOI 10.1007/s11307-007-0078-3

    View details for Web of Science ID 000246175500003

    View details for PubMedID 17294333

  • Relative lung perfusion distribution in normal lung scans: observations and clinical implications. Congenital heart disease Cheng, C. P., Taur, A. S., Lee, G. S., Goris, M. L., Feinstein, J. A. 2006; 1 (5): 210-216

    Abstract

    While relative lung perfusion distributions are cited in clinical decision making for congenital and acquired pulmonary vascular diseases, normal values and ranges have not been published for a large population of normally perfused lungs. These values of normal relative perfusion will be useful for establishing what is abnormal and for clinical decisions related to various pulmonary vascular diseases.Relative perfusion distributions were quantified for the top, middle, and bottom thirds of the right and left lungs with a semiautomatic algorithm in 206 normal scintigraphy lung studies (45 +/- 18 years, 149 female, 57 male) acquired between January 1, 2000 and March 30, 2004 in the Nuclear Medicine Division at Stanford Hospital and Clinics.The perfusion data were found to be highly non-Gaussian in nature (necessitating the use of Wilcoxon statistical comparisons), and the right/left perfusion ratio was found to be 52.5/47.5 (+/-2.1%) rather than the often quoted 55/45 split. While this right/left split was consistent between the genders, males had proportionally less perfusion in the lower left lung as compared with females (P < .05).The long-standing 55/45 right/left perfusion ratio assumption was found to be more than 1 standard deviation greater than the mean, and the population variance is very small. Relative pulmonary perfusion distribution varies significantly with lung region, gender, and age, and should be considered when making clinical decisions based on pulmonary perfusion.

    View details for DOI 10.1111/j.1747-0803.2006.00037.x

    View details for PubMedID 18377528

  • Phase I study of I-131-chimeric(ch) TNT-1/B monoclonal antibody for the treatment of advanced colon cancer CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS Street, H. H., Goris, M. L., Fisher, G. A., Wessels, B. W., Cho, C., Hernandez, C., Zhu, H. J., Zhang, Y., Nangiana, J. S., Shan, J. S., Roberts, K., Knox, S. J. 2006; 21 (3): 243-256

    Abstract

    The primary aim of this study was to evaluate the biodistribution and toxicity of 131I-chimeric(ch) TNT-1/B monoclonal antibody (MAB), which binds to intracellular antigens of necrotic regions within tumors, in patients with advanced colon or colorectal cancer. The rationale for targeting areas of tumor necrosis is the observation that necrotic lesions are more abundant in cancer lesions than in surrounding tissues.Cohorts of patients with advanced colon or colorectal cancer were administered a one-time 30-60-minute intravenous (i.v.) infusion of 131I-chTNT-1/B at doses ranging from 12.95 to 66.23 MBq/kg (0.35-1.79 mCi/kg).The dose-limiting toxicity, experienced at 66.23 MBq/kg (1.79 mCi/kg) 131I-chTNT-1/B MAB, was myelosuppression. Two (2) patients at the 66.23-MBq/kg (1.79 mCi/kg) dose level had both grade 3 thrombocytopenia and grade 3 neutropenia that persisted for at least 2 weeks but were reversible. The maximum tolerated dose was 58.09 MBq/kg (1.57 mCi/kg) 131I-chTNT-1/B MAB. Of the 21 patients, one developed a moderate human antichimeric antibody (HACA) response and 6 developed low HACA responses.The infusion of 131I-chTNT-1/B MAB was well tolerated, without significant nonhematological toxicity. No patient obtained a complete or partial response, based on tumor cross-product response criteria. Tumor localization was seen in patients with dose levels at, and exceeding, 50.23 MBq/kg (1.36 mCi/kg) 131I-chTNT-1/B MAB.

    View details for Web of Science ID 000239162600010

    View details for PubMedID 16918301

  • Tc-99-HYNIC-annexin VSPECT imaging of acute stroke and its response to neuroprotective therapy with anti-Fas ligand antibody EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Blankenberg, F. G., Kalinyak, J., Liu, L. P., Koike, M., Cheng, D. Y., Goris, M. L., Green, A., Vanderheyden, J. L., Tong, D. C., Yenari, M. A. 2006; 33 (5): 566-574

    Abstract

    The first aim of the study was to determine whether (99m)Tc-HYNIC-annexin V, a marker of cellular stress and apoptosis, can detect ischemic injury in patients with acute stroke. Secondly, we wished to test radiolabeled annexin's ability to monitor therapy in a rodent model of focal ischemic injury.SPECT imaging of patients was performed between 1 and 2 h after intravenous injection of 30 mCi (1,110 MBq) of tracer. Eight MFL4 (anti-FasL) antibody-treated (400 microg i.p. days 0 and 3) and 21 control adult male Sprague-Dawley rats underwent small animal SPECT imaging with 5-10 mCi (185-370 MBq) of tracer, 1 and 6 days after a 2-h intraluminal thread occlusion of the left middle cerebral artery.Two patients with acute stroke had regions of multifocal annexin uptake that correlated with sites of restricted diffusion on MRI. Anti-FasL antibody treatment significantly reduced annexin uptake by 92% with a 60% decrease in the number of caspase-8 staining (apoptotic) neurons on day 1. On day 6, treated animals had an 80% reduction in tracer uptake with a 75% decrease in infarct size as compared with controls. Annexin uptake in controls and treated animals (day 6) linearly correlated with infarct size (r (2)=0.603, p=0.0036) and the number of TUNEL-positive (apoptotic) nuclei (r (2)=0.728, p=0.00084).Annexin imaging shows foci of increased uptake at sites of ischemic injury in patients with acute stroke. Annexin imaging can assess the effects of therapy for ischemic cerebral injury in rats, suggesting its potential as a non-invasive indicator of drug efficacy in future clinical trials.

    View details for DOI 10.1007/s00259-005-0046-6

    View details for PubMedID 16477433

  • Bioluminescent-inescent monitoring of NIS-mediated I-131 ablative effects in MCF-7 Xenografts MOLECULAR IMAGING Ghosh, M., Gambhir, S. S., De, A., Nowels, K., Goris, M., Wapnir, I. 2006; 5 (2): 76-84

    Abstract

    Optical imaging has made it possible to monitor response to anticancer therapies in tumor xenografts. The concept of treating breast cancers with (131)I is predicated on the expression of the Na(+)/I- symporter (NIS) in many tumors and uptake of I- in some. The pattern of (131)I radioablative effects were investigated in an MCF-7 xenograft model dually transfected with firefly luciferase and NIS genes. On Day 16 after tumor cell implantation, 3 mCi of (131)I was injected. Bioluminescent imaging using d-luciferin and a cooled charge-coupled device camera was carried out on Days 1, 2, 3, 7, 10, 16, 22, 29, and 35. Tumor bioluminescence decreased in (131)I-treated tumors after Day 3 and reached a nadir on Day 22. Conversely, bioluminescence steadily increased in controls and was 3.85-fold higher than in treated tumors on Day 22. Bioluminescence in (131)I-treated tumors increased after Day 22, corresponding to tumor regrowth. By Day 35, treated tumors were smaller and accumulated 33% less (99m)TcO(4)(-) than untreated tumors. NIS immunoreactivity was present in <50% of (131)I-treated cells compared to 85-90% of controls. In summary, a pattern of tumor regression occurring over the first three weeks after (131)I administration was observed in NIS-expressing breast cancer xenografts.

    View details for DOI 10.2310/7290.2006.00008

    View details for PubMedID 16954021

  • Dornase alfa reduces air trapping in children with mild cystic fibrosis lung disease - A quantitative analysis CHEST Robinson, T. E., Goris, M. L., Zhu, H. J., Chen, X. R., Bhise, F., Sheikh, F., Moss, R. B. 2005; 128 (4): 2327-2335

    Abstract

    To evaluate quantitative air trapping measurements in children with mild cystic fibrosis (CF) lung disease during a 1-year, double-blind, placebo-controlled, recombinant human deoxyribonuclease (rhDNase) [dornase alfa] intervention trial and compare results from quantitative air trapping with those from spirometry or visually scored high-resolution CT (HRCT) scans of the chest.Twenty-five children with CF randomized to either daily rhDNase or placebo aerosol were evaluated at baseline, and at 3 months and 12 months by spirometer-triggered HRCT and spirometry. Outcome variables were percentage of predicted FVC, FEV1, and forced expiratory flow, midexpiratory phase (FEF(25-75%)); total and subcomponent visual HRCT scores; and quantitative air trapping measurements derived from chest HRCT images.At baseline, there were no statistical differences between groups in any of the variables used as an outcome. After 3 months of treatment, both groups had improvements in percentage of predicted FEV1 and FEF(25-75%), and total HRCT visual scores. In contrast, the rhDNase group had a 13% decrease in quantitative air trapping from baseline (severe air trapping [A3]), compared to an increase of 48% in the placebo group (p = 0.023). After 12 months, both groups had declines in percentage of predicted FVC and FEV1, but the rhDNase group retained improvements in percentage of predicted FEF(25-75%) and quantitative air trapping. The mucus plugging and total HRCT visual scores were also improved in the rhDNase group after 12 months of treatment, with and without significant differences between groups (p = 0.026 and p = 0.676). Quantitative air trapping (A3) remained improved in the rhDNase group (- 15.4%) and worsened in the placebo group (+61.3%) with nearly significant differences noted between groups (p = 0.053) after 12 months of treatment.Quantitative air trapping is a more consistent sensitive outcome measure than either spirometry or total HRCT scores, and can discriminate differences in treatment effects in children with minimal CF lung disease.

    View details for Web of Science ID 000232679400063

    View details for PubMedID 16236891

  • The radioisotope contributes significantly to the activity of radioimmunotherapy CLINICAL CANCER RESEARCH Davis, T. A., Kaminski, M. S., Leonard, J. P., Hsu, F. J., Wilkinson, M., Zelenetz, A., Wahl, R. L., KROLL, S., Coleman, M., Goris, M., Levy, R., Knox, S. J. 2004; 10 (23): 7792-7798

    Abstract

    A multicenter, randomized study was undertaken to estimate the single agent activity of Tositumomab and to determine the contribution of radioisotope-labeling with (131)I to activity and toxicity by comparing treatment outcomes for Tositumomab and Iodine I 131 Tositumomab (BEXXAR) to an equivalent total dose of unlabeled Tositumomab.Seventy-eight patients with refractory/relapsed non-Hodgkin's lymphoma were randomized to either unlabeled Tositumomab or Iodine I 131 Tositumomab. Patients progressing after unlabeled Tositumomab could cross over to receive Iodine I 131 Tositumomab. The median follow-up at analysis was 42.6 months (range 1.9 to 71.5 months).Responses in the Iodine I 131 Tositumomab versus unlabeled Tositumomab groups: overall response 55% versus 19% (P = 0.002); complete response 33% versus 8% (P = 0.012); median duration of overall response not reached versus 28.1 months (95% confidence interval: 7.6, not reached); median duration of complete response not reached in either arm; and median TTP 6.3 versus 5.5 months (P = 0.031), respectively. Of the patients who had a complete response after initial Iodine I 131 Tositumomab therapy, 71% (10 of 14) continued in complete response at 29.8 to 71.1 months. Two patients who achieved a complete response after unlabeled Tositumomab had ongoing responses at 48.1 to 56.9 months. Nineteen patients received Iodine I 131 Tositumomab crossover therapy. Responses after crossover versus prior response to unlabeled Tositumomab were as follows: complete response rates of 42% versus 0% (P = 0.008); overall response 68% versus 16% (P = 0.002); median durations of overall response 12.6 versus 7.6 months (P = 0.001); and median TTP 12.4 versus 5.5 months (P = 0.01), respectively. Hematologic toxicity was more severe and nonhematologic adverse events were more frequent after Iodine I 131 Tositumomab than after Tositumomab alone. Elevated thyrotropin occurred in 5% of patients. Seroconversion to human antimurine antibody after Iodine I 131 Tositumomab, unlabeled Tositumomab, and Iodine I 131 Tositumomab-crossover was 27%, 19%, and 0%, respectively.Unlabeled Tositumomab showed single agent activity, but in this direct comparison, all of the therapeutic outcome measures were significantly enhanced by the conjugation of (131)I to Tositumomab.

    View details for Web of Science ID 000225673200002

    View details for PubMedID 15585610

  • Pericardial lymph node involvement in lymphoma as identified on PET CLINICAL NUCLEAR MEDICINE Franc, B., Yoshida, E., Herfkens, R., Goris, M. 2004; 29 (11): 741-742

    View details for PubMedID 15483497

  • The Na+/I- symporter mediates iodide uptake in breast cancer metastases and can be selectively down-regulated in the thyroid CLINICAL CANCER RESEARCH Wapnir, I. L., Goris, M., Yudd, A., Dohan, O., Adelman, D., Nowels, K., Carrasco, N. 2004; 10 (13): 4294-4302

    Abstract

    The Na(+)/I(-) symporter (NIS) is a key plasma membrane protein that mediates active iodide (I(-)) transport in the thyroid, lactating breast, and other tissues. Functional NIS expression in thyroid cancer accounts for the longstanding success of radioactive iodide ((131)I) ablation of metastases after thyroidectomy. Breast cancer is the only other cancer demonstrating endogenous functional NIS expression. Until now, NIS activity in breast cancer metastases (BCM) was unproven.Twenty-seven women were scanned with (99m)TcO(4)(-) or (123)I(-) to assess NIS activity in their metastases. An (131)I dosimetry study was offered to patients with I(-)-accumulating tumors. Selective down-regulation of thyroid NIS was tested in 13 patients with T(3) and in one case with T(3) + methimazole (MMI; blocks I(-) organification). NIS expression was evaluated in index and/or metastatic tumor samples by immunohistochemistry.I(-) uptake was noted in 25% of NIS-expressing tumors (two of eight). The remaining cases did not show NIS expression or activity. Thyroid I(-) uptakes were decreased to

    View details for PubMedID 15240514

  • Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin lymphoma BLOOD Forero, A., Weiden, P. L., Vose, J. M., Knox, S. J., LoBuglio, A. F., Hankins, J., Goris, M. L., Picozzi, V. J., Axworthy, D. B., Breitz, H. B., Sims, R. B., Ghalie, R. G., Shen, S., Meredith, R. F. 2004; 104 (1): 227-236

    Abstract

    Pretargeted radioimmunotherapy (PRIT) has the potential to increase the dose of radionuclide delivered to tumors while limiting radiation to normal tissues. The purpose of this phase 1 trial is to assess safety of this multistep approach using a novel tetrameric single-chain anti-CD20-streptavidin fusion protein (B9E9FP) as the targeting moiety in patients with B-cell non-Hodgkin lymphoma (NHL), and to characterize its pharmacokinetics and immunogenicity. All patients received B9E9FP (160 mg/m(2) or 320 mg/m(2)); either 48 or 72 hours later, a synthetic clearing agent (sCA) was administered (45 mg/m(2)) to remove circulating unbound B9E9FP. (90)Yttrium ((90)Y; 15 mCi/m(2))/(111)In (5 mCi)-DOTA-biotin was injected 24 hours later. There were 15 patients enrolled in the study. B9E9FP had a mean plasma half-life (T(1/2)) of 25 +/- 6 hours with a reduction in plasma level of more than 95% within 6 hours of sCA administration. (90)Y/(111)In-DOTA-biotin infusion resulted in rapid tumor localization and urinary excretion. The ratio of average tumor to whole-body radiation dose was 49:1. No significant hematologic toxicities were noted in 12 patients. There were 2 patients who had hematologic toxicity related to progressive disease. There were 2 complete remissions (90 and 325 days) and one partial response (297 days). B9E9FP performs well as the targeting component of PRIT with encouraging dosimetry, safety, and efficacy. A dose escalation trial of (90)Y-DOTA-biotin in this format is warranted.

    View details for DOI 10.1182/blood-2003-09-3284

    View details for Web of Science ID 000222307500042

    View details for PubMedID 14996706

  • Dosimetry model for radioactivity localized to intestinal mucosa CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS Fisher, D., Rajon, D., Breitz, H., Goris, M., Bolch, W., Knox, S. 2004; 19 (3): 293-307

    Abstract

    This paper provides a new model for calculating radiation-absorbed doses to the full thickness of the small and large intestinal walls, and to the mucosal layers. The model was used to estimate the intestinal radiation doses from yttrium-90-labeled-DOTA-biotin binding to NR-LU-10-streptavidin in patients.We selected model parameters from published data and observations, and used the model to calculate energy-absorbed fractions using the EGS4 radiation transport code. We determined the cumulated (90)Y activity in the small and large intestines of patients from gamma camera images, and calculated absorbed doses to the mucosal layer and to the whole intestinal wall.The mean absorbed dose to the wall of the small intestine was 16.2 mGy/MBq (60 cGy/mCi) administered from (90)Y localized in the mucosa, and 70 mGy/MBq (260 cGy/mCi) to the mucosal layer within the wall. Doses to the large intestinal wall and to the mucosa of the large intestine were lower than those for the small intestine by a factor of about 2.5. These doses are greater by factors of about 5 to 6 than those that would have been calculated using the standard MIRD models that assume the intestinal activity is in the bowel contents.The specific uptake of radiopharmaceuticals in mucosal tissues may lead to dose-related intestinal toxicities. Tissue dosimetry at the sub-organ level is useful for a better understanding of intestinal tract radiotoxicity and associated dose-response relationships.

    View details for Web of Science ID 000222672600004

    View details for PubMedID 15285876

  • Detection of focal hypoxic-ischemic injury and neuronal stress in a rodent model of unilateral MCA occlusion/reperfusion using radiolabeled annexin V EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Mari, C., Karabiyikoglu, M., Goris, M. L., Tait, J. F., Yenari, M. A., Blankenberg, F. G. 2004; 31 (5): 733-739

    Abstract

    In this study we wished to determine whether technetium-99m annexin V, an in vivo marker of cellular injury and death, could be used to noninvasively monitor neuronal injury following focal middle cerebral artery (MCA) occlusion/reperfusion injury. Sixteen adult male Sprague-Dawley rats (along with four controls) underwent left (unilateral) MCA intraluminal beaded thread occlusion for 2 h followed by reperfusion. One hour following tail vein injection of 5-10 mCi of (99m)Tc-annexin V, animals underwent either single-photon emission computerized tomography (SPECT) or autoradiography followed by immunohistochemical analyses. There was abnormal, bilateral, multifocal uptake of (99m)Tc-annexin V in each cerebral hemisphere as seen by both SPECT and autoradiography at 4 h and 1, 3, and 7 days after initiation of occlusion. The average maximal annexin V uptake at 4 h was 310%+/-85% and 365%+/-151% above control values (P<0.006) within the right and left hemispheres, respectively, peaking on day 3 with values of 925%+/-734% and 1,194%+/-643% (P<0.03) that decreased by day 7 to 489%+/-233% and 785%+/-225% (P<0.01). Total lesional volume of the left hemisphere was 226%, 261%, and 451% ( P<0.03) larger than the right at 4, 24, and 72 h after injury, respectively. Annexin V localized to the cytoplasm of injured neurons ipsilateral to the site of injury as well as to otherwise normal-appearing neurons of the contralateral hemisphere as confirmed by dual fluorescent microscopy. It is concluded that there is abnormal bilateral, multifocal annexin V uptake, greater on the left than on the right side, within 4 h of unilateral left MCA ischemic injury and that the uptake peaks at 3 days and decreases by 7 days after injury. This pattern suggests that neuronal stress may play a role in the response of the brain to focal injury and be responsible for annexin V uptake outside the region of ischemic insult.

    View details for DOI 10.1007/s00259-004-1473-5

    View details for PubMedID 14985868

  • Performance of intravascular probe in animal studies IEEE Nuclear Science Symposium/Medical Imaging Conference Yamaguchi, Y., Patt, B. E., Iwanczyk, J. S., MacDonald, L. M., Mari, C., Goris, M. L., Strauss, H. W., Janecek, M., Hoffman, E., Ghazarossian, V. IEEE. 2004: 2463–2467
  • Long-term results of a randomized trial comparing Tositumomab and Iodine-131 Tositumomab (BEXXAR (R)) with Tositumomab alone in patients with relapsed or refractory low-grade (LG) or transformed low grade (T-LG) Non-Hodgkin's Lymphoma (NHL). 45th Annual Meeting and Exhibition of the American-Society-of-Hematology Davis, T., Kaminski, M. S., Leonard, J. P., Hsu, F. J., Wilkinson, M., Wahl, R., Coleman, M., Goris, M., Levy, R., Knox, S. AMER SOC HEMATOLOGY. 2003: 405A–406A
  • Higher doses of Rituxan (R) alter pharmacokinetics and biodistribution of Zevalin (R) but may increase responses; a preliminary report of a phase I study of Zevalin (R) using a modified treatment regimen for relapsed or refractory CD20+B-cell follicular/transformed non-Hodgkin's lymphoma. 45th Annual Meeting and Exhibition of the American-Society-of-Hematology Forero-Torres, A., Besh, S., Knox, S., Micallef, I., Wiseman, G., Witzig, T., Lobuglio, A., Shen, S., Goris, M., CARPENTER, M., Meredith, R. AMER SOC HEMATOLOGY. 2003: 408A–408A
  • An automated approach to quantitative air trapping measurements in mild cystic fibrosis CHEST Goris, M. L., Zhu, H. Y., Blankenberg, F., Chan, F., Robinson, T. E. 2003; 123 (5): 1655-1663

    Abstract

    To automatically derive the degree of air trapping in mild cystic fibrosis (CF) disease from high-resolution CT (HRCT) data, and to evaluate the discriminating power of the measurement.The data consist of six pairs of anatomically matched tomographic slices, obtained during breath-holding in triggered HRCT acquisitions. The pairs consist of an inspiratory slice, at > or = 95% of slow vital capacity, and an expiratory slice at near residual volume (nRV). The subjects are 25 patients with mild CF and 10 age-matched, normal control subjects.Lung segmentation is automatic. The limits defining air trapping in the expiratory slices are determined by the distribution of densities in the expanded lung. They are modulated by density changes between expiration and inspiration. Air trapping defects consist of contiguous low-density voxels. The difference between patients and control subjects was evaluated in comparison to pulmonary function test (PFT) results and lung density distribution descriptors (global density descriptors).In mild CF, air trapping does not correlate with global PFT results, except for the ratio of residual volume (RV) to total lung capacity (TLC); however, the size of air trapping defects was the best discriminator between patients and control subjects (p < 0.005). Of PFT results, only RV/TLC reached significance at p < 0.05. The global density descriptors reached near significance in the nRV images only.Air trapping defined as defect size and measured in an objective automated manner is a powerful discriminator for mild CF.

    View details for PubMedID 12740287

  • Positively labeled white blood cell scan with eosinophilia and absence of infection CLINICAL NUCLEAR MEDICINE Vasanawala, M. S., Goris, M. L. 2003; 28 (5): 389-391

    Abstract

    The authors describe the variability of Tc-99m exametazime-labeled leukocyte distribution as a function of the relative frequency of white cell types in the labeled blood.A 76-year-old man who was hospitalized with fever and possible postoperative osteomyelitis underwent scintigraphic imaging with Tc-99m exametazime-labeled leukocytes.The white cell scan excluded any discrete focus of infection and revealed diffuse involvement of the lymph nodes and skin. The pathologic diagnosis was angioimmunoblastic T-cell lymphoma. The atypical infiltrates seen on the white cell scan can be explained by the severe eosinophilic blood count on the day of leukocyte labeling (total leukocyte count: 8,100 cells/microl with 63% neutrophils, 8.9% lymphocytes, and 22.2% eosinophils).In the labeling of the leukocyte moiety, a higher presence of any leukocyte subpopulation will modify the biodistribution and thus the image interpretation.

    View details for PubMedID 12702935

  • Application of dedicated small animal SPECT: Radiolabeled annexin V tomographic imaging of ischemic reperfusion injury in the rat brain. 50th Annual Meeting of the Society-of-Nuclear-Medicine Mari, C., Yenari, M., Tait, J. F., Zhu, J. H., Goris, M. L., Blankenberg, F. G. SOC NUCLEAR MEDICINE INC. 2003: 215P–215P
  • Therapeutic lymphangiogenesis with human recombinant VEGF-C. FASEB journal Szuba, A., Skobe, M., Karkkainen, M. J., Shin, W. S., Beynet, D. P., Rockson, N. B., Dakhil, N., Spilman, S., Goris, M. L., Strauss, H. W., Quertermous, T., Alitalo, K., Rockson, S. G. 2002; 16 (14): 1985-1987

    Abstract

    Chronic regional impairments of the lymphatic circulation often lead to striking architectural abnormalities in the lymphedematous tissues. Lymphedema is a common, disabling disease that currently lacks a cure. Vascular endothelial growth factors C and D mediate lymphangiogenesis through the VEGFR-3 receptor on lymphatic endothelia. The purpose of this study was to investigate the therapeutic potential for lymphangiogenesis with VEGF-C. We developed a rabbit ear model to simulate human chronic postsurgical lymphatic insufficiency. Successful, sustained surgical ablation of the ear lymphatics was confirmed by water displacement volumetry. After complete healing, the experimental animals (n=8) received a single, s.c. 100 microg dose of VEGF-C in the operated ear; controls (n=8) received normal saline. Radionuclide lymphoscintigraphy was performed to quantitate lymphatic function. Immunohistochemistry (IHC) was performed 7-8 days following treatment. After VEGF-C, there was a quantifiable amelioration of lymphatic function. IHC confirmed a significant increase in lymphatic vascularity, along with reversal of the intense tissue hypercellularity of untreated lymphedema. This study confirms the capacity of a single dose of VEGF-C to induce therapeutic lymphangiogenesis in acquired lymphedema. In addition to improving lymphatic function and vascularity, VEGF-C can apparently reverse the abnormalities in tissue architecture that accompany chronic lymphatic insufficiency.

    View details for PubMedID 12397087

  • Low uptake of Tc-99m tetrofosmin in lung cancer - A case report CLINICAL NUCLEAR MEDICINE Franc, B., Goris, M. 2002; 27 (10): 698-700

    Abstract

    Technetium-99m tetrofosmin has been used as a tumor-imaging agent in cases of lung cancer. The authors present a case showing a lung tumor that concentrated Tl-201 distinctly more than Tc-99m tetrofosmin during a dual-isotope cardiac examination. A brief review of the literature is provided and possible explanations for this difference in tracer uptake are discussed.

    View details for DOI 10.1097/01.RLU.0000027801.86894.5D

    View details for PubMedID 12352109

  • Therapeutic lymphangiogenesis with human recombinant VEGF-C FASEB JOURNAL Szuba, A., Skobe, M., Karkkainen, M. J., Shin, W. S., Beynet, D. P., Rockson, N. B., Dakhil, N., Spilman, S., Goris, M. L., Strauss, H. W., Quertermous, T., Alitalo, K., Rockson, S. G. 2002; 16 (12): 1985-?

    Abstract

    Chronic regional impairments of the lymphatic circulation often lead to striking architectural abnormalities in the lymphedematous tissues. Lymphedema is a common, disabling disease that currently lacks a cure. Vascular endothelial growth factors C and D mediate lymphangiogenesis through the VEGFR-3 receptor on lymphatic endothelia. The purpose of this study was to investigate the therapeutic potential for lymphangiogenesis with VEGF-C. We developed a rabbit ear model to simulate human chronic postsurgical lymphatic insufficiency. Successful, sustained surgical ablation of the ear lymphatics was confirmed by water displacement volumetry. After complete healing, the experimental animals (n=8) received a single, s.c. 100 microg dose of VEGF-C in the operated ear; controls (n=8) received normal saline. Radionuclide lymphoscintigraphy was performed to quantitate lymphatic function. Immunohistochemistry (IHC) was performed 7-8 days following treatment. After VEGF-C, there was a quantifiable amelioration of lymphatic function. IHC confirmed a significant increase in lymphatic vascularity, along with reversal of the intense tissue hypercellularity of untreated lymphedema. This study confirms the capacity of a single dose of VEGF-C to induce therapeutic lymphangiogenesis in acquired lymphedema. In addition to improving lymphatic function and vascularity, VEGF-C can apparently reverse the abnormalities in tissue architecture that accompany chronic lymphatic insufficiency.

    View details for DOI 10.1096/fj.02-0401fje

    View details for Web of Science ID 000179167600007

  • Pretarget radioimmunotherapy (RIT) with anti-CD20 fusion protein in patients with non-Hodgkin's lymphoma (NHL). Meredith, R., Shen, S., Breitz, H., Fisher, D., Goris, M., Knox, S., Hankins, J., Vose, J., Picozzi, V. SOC NUCLEAR MEDICINE INC. 2002: 116P–117P
  • Therapeutic lymphangiogenesis in a rabbit ear model of chronic post-surgical lymphatic insufficiency Szuba, A., Skobe, M., Shin, W., Beynet, D. P., Rockson, N. B., Dakhil, N., Goris, M. L., Strauss, H. W., Quertermous, T., Alitalo, K., Rockson, S. G. FEDERATION AMER SOC EXP BIOL. 2002: A516–A516
  • A model for chronic, post-surgical lymphatic insufficiency Shin, W., Szuba, A., Skobe, M., Beynet, D. P., Rockson, N. B., Dakhil, N., Goris, M. L., Strauss, H. W., Quertermous, T., Alitalo, K., Rockson, S. G. FEDERATION AMER SOC EXP BIOL. 2002: A123–A124
  • A model of acute, post-surgical lymphedema Beynet, D. P., Szuba, A., Skobe, M., Rockson, N. B., Dakhil, N., Shin, W., Goris, M. L., Strauss, H. W., Quertermous, T., Alitalo, K., Rockson, S. G. FEDERATION AMER SOC EXP BIOL. 2002: A124–A124
  • Interhemispheric asymmetry of regional cerebral blood flow in prepubescent boys with attention deficit hyperactivity disorder NUCLEAR MEDICINE COMMUNICATIONS Langleben, D. D., Austin, G., Krikorian, G., Ridlehuber, H. W., Goris, M. L., Strauss, H. W. 2001; 22 (12): 1333-1340

    Abstract

    The prefrontal cortex is asymmetric in both structure and function. In normal subjects, the right prefrontal cortex is activated more than the left during response inhibition. Patients with attention deficit hyperactivity disorder (ADHD) have impaired response inhibition and altered structural interhemispheric asymmetry. This study was conducted to examine the functional interhemispheric asymmetry during response inhibition in children with ADHD. Subjects were divided into three groups according to the level of motor hyperactivity. Blood flow tracer (99m)Tc-ethyl cysteinate dimer was injected while subjects were performing a response inhibition task (RIT), followed by single photon emission computerized tomography (SPECT). After three-dimensional reconstruction, filtering and smoothing, individual scans were morphed to a template. Three average group images were created from individual scans. Each average group image was subtracted voxel-by-voxel from its mirror image to compare the regional cerebral blood flow (rCBF) in the right and left cerebral hemispheres, yielding images of significant interhemispheric rCBF asymmetry. The severe hyperactivity group exhibited most prefrontal left>right rCBF asymmetry and left>right occipitoparietal asymmetry. Reversal of functional prefrontal asymmetry in boys with severe motor hyperactivity supports the hypothesis of right prefrontal cortex dysfunction in ADHD.

    View details for Web of Science ID 000172475200009

    View details for PubMedID 11711904

  • In vivo Imaging of acute cardiac rejection in human patients using (99m)Technetium labeled annexin V AMERICAN JOURNAL OF TRANSPLANTATION Kown, M. H., Strauss, H. W., Blankenberg, F. G., Berry, G. J., Stafford-Cecil, S., Tait, J. F., Goris, M. L., Robbins, R. C. 2001; 1 (3): 270-277

    Abstract

    Annexin V binds phosphatidylserine moieties on apoptotic cells. This study reports the initial experience at Stanford University Medical Center with 99mTc-labeled annexin V imaging as a noninvasive measure of apoptosis in acute cardiac rejection. Ten cardiac transplant patients had 99mTc Annexin V imaging and endomyocardial biopsy (EMB) performed within 24 h. No complications related to 99mTc annexin V administration occurred. Eight patients had ISHLT grade of acute rejection of 1A or less. Five patients had two or more areas of uptake noted in the right ventricle on imaging studies. Two of these patients had positive biopsies: one patient had grade 2 rejection with two focal uptake areas and another had grade 3A rejection with three foci. An additional five patients had either one or zero hot spot areas and corresponding negative EMBs. 99mTc-annexin V appears to be well tolerated and may identify patients with acute cardiac rejection.

    View details for Web of Science ID 000173466800011

    View details for PubMedID 12102261

  • Three-Dimensional Quantitative Analysis of Scintigraphic Tomographic Images after Elastic Transformation to a Template. Surgical technology international Goris, M. L., Maclean, M., Pace, W. M., Yee, A., Kwan, A. 2000; IX: 81-90

    Abstract

    The diagnostic information in scintigraphic images is generally not contained in specific morphological image attributes, but in the regional distribution of count rate densities across the organ volumes. In a subclass of scintigraphic images, the evaluation is actually based on a dual comparison.

    View details for PubMedID 12219283

  • Phase II trial of yttrium-90-DOTA-biotin pretargeted by NR-LU-10 antibody/streptavidin in patients with metastatic colon cancer CLINICAL CANCER RESEARCH Knox, S. J., Goris, M. L., Tempero, M., Weiden, P. L., Gentner, L., Breitz, H., ADAMS, G. P., Axworthy, D., Gaffigan, S., Bryan, K., Fisher, D. R., Colcher, D., Horak, I. D., Weiner, L. M. 2000; 6 (2): 406-414

    Abstract

    A Phase II study of yttrium-90-tetra-azacyclododecanetetra-acetic acid-biotin (90Y-DOTA-biotin) pretargeted by NR-LU-10 antibody/streptavidin (SA) was performed. The primary objectives of the study were to evaluate the efficacy and safety of this therapy in patients with metastatic colon cancer. Twenty-five patients were treated with a single dose of 110 mCi/m2 (mean administered dose, 106.5 +/- 10.3 mCi/m2) of 90Y-DOTA-biotin. There were three components of the therapy. Patients first received NR-LU-10/SA on day 1. A clearing agent (biotin-galactose-human serum albumin) was administered approximately 48 h after the NR-LU-10/SA to remove residual circulating unbound NR-LU-10/SA. Lastly, 24 h after administration of clearing agent, patients received biotin-DOTA-labeled with 110 mCi/m2 90Y. All three components of the therapy were administered i.v. Both hematological and nonhematological toxicities were observed. Diarrhea was the most frequent grade 4 nonhematological toxicity (16%; with 16% grade 3 diarrhea). Hematological toxicity was less severe with 8% grade 3 and 8% grade 4 neutropenia and 8% grade 3 and 16% grade 4 thrombocytopenia. The overall response rate was 8%. Two partial responders had freedom from progression of 16 weeks. Four patients (16%) had stable disease with freedom from progression of 10-20 weeks. Despite the relatively disappointing results of this study in terms of therapeutic efficacy and toxicity, proof of principle was obtained for the pretargeting approach. In addition, valuable new information was obtained about normal tissue tolerance to low-dose-rate irradiation that will help to provide useful guidelines for future study designs.

    View details for Web of Science ID 000085502600013

    View details for PubMedID 10690517

  • [Preliminary evaluation of the effect of an attenuation correction method in myocardial perfusion SPECT]. Revista espanola de medicina nuclear Cortés-Blanco, A., Fujii, C., Goris, M. L. 1999; 18 (6): 416-424

    Abstract

    We propose a method to assess an attenuation correction method in myocardial perfusion SPECT. Three types of images are obtained: one resulting from a classic acquisition and filtered back-projection (classic), and those resulting from acquisition with a transmission source and an iterative reconstruction, with (music) or without (hybrid) the attenuation correction factored in to compare the three types of images and classify them as normal or abnormal, a three dimensional inter-patient quantitative comparison method was used. Differences were computed as fractions of the myocardial volume in which density differences are significant by population standards. In 7 cases the cumulative difference between prone and supine in hybrid images was 124 and 45 in music images. In 10 cases the cumulative difference between classic vs music images was 279, and between classic and hybrid 86. The AC changed 4/12 cases from abnormal to normal. The attenuation correction effect was concentrated on the septal and inferior walls, but neither exclusively nor evenly among patients. The attenuation correction effectively minimizes attenuation effects by a factor of 2.7, due to a correction of at least 69%. The correction has a small but substantial effect on the results.

    View details for PubMedID 10611567

  • Radiation absorbed dose estimation for Y-90-DOTA-biotin with pretargeted NR-LU-10/streptavidin CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS Breitz, H. B., Fisher, D. R., Goris, M. L., Knox, S., Ratliff, B., Murtha, A. D., Weiden, P. L. 1999; 14 (5): 381-395

    Abstract

    Pretargeted radioimmunotherapy permits the administration of doses of 90Y five times higher than is possible with antibodies directly labeled with 90Yttrium (90Y). These high doses of 90Y introduced new issues for dosimetry that were not encountered in prior studies using conventional radioimmunotherapy. We have addressed these issues here and correlated dosimetry estimates with observed toxicity and tumor responses.The pretargeted radioimmunotherapy (PRIT) system employed the antibody NR-LU-10 conjugated with streptavidin, a glycoprotein clearing agent and 90Y-DOTA-biotin. A single dose of 90Y was escalated to 140 mCi/m2. Indium-111(111In) (3-5 mCi) DOTA-biotin was co-injected for gamma camera imaging and dosimetry assessment. The effect of bremsstrahlung radiation from increasing 90Y activity levels with a constant dose of 111In was studied using a phantom. Patient images identified the intestinal tract and the kidneys as potential organs at risk of clinically significant radiation toxicity. A method of measuring the activity localized in the intestinal tract was developed, and S values were calculated to estimate intestinal wall dose from radioactivity present in the intestine. Intestinal, bone marrow and renal toxicity were observed. Coefficients were derived for correlating the relationships between observed intestinal and marrow toxicity and the estimated radiation absorbed doses.At an 90Y:111In ratio of 50:1, bremsstrahlung radiation accounted for 12% of the counts in the images. Grade IV diarrhea was observed in patients estimated to have received 6850-14,000 cGy to the large intestinal wall. The correlation coefficient of intestinal toxicity with absorbed dose was 0.64. Myelotoxicity (measured as grade of suppression of absolute neutrophil count) correlated better with marrow dose (r = 0.72) than with the whole body dose, (r = 0.44). Delayed renal toxicity was observed in two patients 8 and 11 months following therapy. Tumor response was seen in the two patients with the highest estimated dose to tumor, 4,000-6,000 cGy.Dosimetry is feasible using 111In as a tracer in the presence of high 90Y activity. The absorbed dose estimates derived in the PRIT schema correlated moderately well with clinically observed toxicity and response.

    View details for Web of Science ID 000083129300007

    View details for PubMedID 10850323

  • Factors affecting and computation of myocardial perfusion reference images NUCLEAR MEDICINE COMMUNICATIONS Goris, M. L., Hotz, B., Thirion, J. P., Similon, P. 1999; 20 (7): 627-635

    Abstract

    Many quantitative analysis methods for myocardial perfusion studies require as a central step a comparison with a 'normal' or average density distribution map or reference image. It has been recognized, however, that the normal distribution can be affected by patient attributes, including sex and weight or body habitus, and by acquisition attributes, including the choice of tracer and the position of the patient during imaging. Some authors have proposed separate reference images for the sexes and the tracer. This approach fails if a large number of binary attributes have to be considered, since one would need 2" reference images for each attribute. The problem is compounded when continuous attributes (e.g. age and weight) are included, especially if the approach is to average separate homogeneous groups for each attribute. We propose to create case-specific reference images for the interpretation of myocardial perfusion studies by creating a model based on the influence of each attribute. From a non-homogeneous population of normal cases, or cases presumed to be normal on the basis of the Diamond and Forrester stratification, the effect of patient and study attributes on the density distribution in the stress image and the density differences between rest and stress images were computed. The effects are computed by multi-linear regression, to account for cross-correlation. Significance is assigned on the basis of a partial Fisher test. The data are myocardial perfusion images matched in 3D to a template by an elastic transformation. Even though there was some cross-correlation in the data, we were able to show independent effects of sex, position (prone or supine), age, weight, tracer combination and stress method (exercise, persantine and adenosine). Taken as a whole, the multi-linear regression demonstrated a significant effect in 72% of the pixels within the myocardial volume. In addition, the distribution predicted by the model was equivalent to average images from homogeneous matched groups. In conclusion, our approach makes it possible to produce case-specific reference images without the need for multiple homogeneous large groups to produce averages for each possible patient or study attribute.

    View details for Web of Science ID 000081454700006

    View details for PubMedID 10423765

  • An integral method for the analysis of wall motion in gated myocardial SPECT studies INFORMATION PROCESSING IN MEDICAL IMAGING, PROCEEDINGS Goris, M. L., Van Uitert, R. L. 1999; 1613: 334-339
  • Pretargeted Radioimmunotherapy (TM) with antibody-streptavidin and Y-90 DOTA-Biotin (Avicidin (R)): Result of a dose escalation study. Breitz, H., Knox, S., Weiden, P., Goris, M., Murtha, A., Bryan, J., Axworthy, D., Seiler, C., Su, F. M., Beaumier, P., Reno, J. SOC NUCLEAR MEDICINE INC. 1998: 71P–71P
  • Pulmonary SPECT imaging and the stripe sign JOURNAL OF NUCLEAR MEDICINE Pace, W. M., Goris, M. L. 1998; 39 (4): 721-723

    Abstract

    A patient with high clinical suspicion for pulmonary embolism underwent a diagnostic scintigraphic ventilation/perfusion scan. The planar images revealed an unmatched perfusion defect with a stripe sign in the right middle lobe. A stripe sign is the appearance of normally perfused tissue between the defect and the pleural surface suggesting a nonpleural-based abnormality. SPECT images acquired in the same study period, however, failed to demonstrate normally perfused tissue between the defect and the pleural surface. Previous studies have compared planar ventilation/perfusion studies with stripe sign perfusion defects to pulmonary angiography. The results suggest that stripe sign perfusion defects are generally not due to emboli. However, planar imaging is projectional and may miss pleural contact in some perfusion lesions depending on the projection. In the absence of SPECT data, the significance of the stripe sign may need to be reassessed.

    View details for Web of Science ID 000072956600040

    View details for PubMedID 9544688

  • Automatic registration and alignment on a template of cardiac stress and rest reoriented SPECT images IEEE TRANSACTIONS ON MEDICAL IMAGING Declerck, J., Feldmar, J., Goris, M. L., Betting, F. 1997; 16 (6): 727-737

    Abstract

    Single photon emission computed tomography (SPECT) imaging with 201Tl or 99mTc agent is used to assess the location or the extent of myocardial infarction or ischemia. A method is proposed to decrease the effect of operator variability in the visual or quantitative interpretation of scintigraphic myocardial perfusion studies. To effect this, the patient's myocardial images (target cases) are registered automatically over a template image, utilizing a nonrigid transformation. The intermediate steps are: 1) Extraction of feature points in both stress and rest three-dimensional (3-D) images. The images are resampled in a polar geometry to detect edge points, which in turn are filtered by the use of a priori constraints. The remaining feature points are assumed to be points on the edges of the left ventricular myocardium. 2) Registration of stress and rest images with a global affine transformation. The matching method is an adaptation of the iterative closest point algorithm. 3) Registration and morphological matching of both stress and rest images on a template using a nonrigid local spline transformation following a global affine transformation. 4) Resampling of both stress and rest images in the geometry of the template. Optimization of the method was performed on a database of 40 pairs of stress and rest images selected to obtain a wide variation of images and abnormalities. Further testing was performed on 250 cases selected from the same database on the basis of the availability of angiographic results and patient stratification.

    View details for Web of Science ID 000072458500004

    View details for PubMedID 9533574

  • MRI of pulmonary embolism using Gd-DTPA-polyethylene glycol polymer enhanced 3D fast gradient echo technique in a canine model MAGNETIC RESONANCE IMAGING Li, K. C., Pelc, L. R., NAPEL, S. A., Goris, M. L., Lin, D. T., SONG, C. K., Leung, A. N., Rubin, G. D., HOLLETT, M. D., Harris, D. P. 1997; 15 (5): 543-550

    Abstract

    This study was to evaluate the accuracy of MR angiography (MRA) using a Gd-DTPA-polyethylene glycol polymer (Gd-DTPA-PEG) with a 3D fast gradient echo (3D fgre) technique in diagnosing pulmonary embolism in a canine model. Pulmonary emboli were created in six mongrel dogs (20-30 kg) by injecting tantalum oxide-doped autologous blood clots into the femoral veins via cutdowns. MRI was performed with a 1.5 T GE Signa imager using a 3D fgre sequence (11.9/2.3/15 degrees) following intravenous injection of 0.06 mmol Gd/kg of Gd-DTPA-PEG. The dogs were euthanized and spiral CT of the lungs were then obtained on the deceased dogs. The MRI images were reviewed independently and receiver-operating-characteristic (ROC) curves were used for statistical analysis using spiral CT results as the gold standard. The pulmonary emboli were well visualized on spiral CT. Out of 108 pulmonary segments in the six dogs, 24 contained emboli >2 mm and 27 contained emboli < or = 2 mm. With unblinded review, MRI detected 79% of emboli >2 mm and only 48% of emboli < or = 2 mm. The blinded review results were significantly worse. Gd-DTPA-PEG enhanced 3D fgre MRI is potentially able to demonstrate pulmonary embolism with fairly high degree of accuracy, but specialized training for the interpretations will be required.

    View details for Web of Science ID A1997XM76800004

    View details for PubMedID 9253998

  • Left ventricular ejection fraction from gated SPET myocardial perfusion studies: A method based on the radial distribution of count rate density across the myocardial wall EUROPEAN JOURNAL OF NUCLEAR MEDICINE Everaert, H., Franken, P. R., Flamen, P., Goris, M., Momen, A., Bossuyt, A. 1996; 23 (12): 1628-1633

    Abstract

    Left ventricular ejection fraction (LVEF) can be derived from gated single-photon emission tomographic (SPET) myocardial perfusion studies using either manual or edge detection techniques. In the presence of severe perfusion defects, however, difficulties may be encountered. In this article a method based on the assumption that the average position of the myocardial wall can be localized by means of statistical analysis of the distribution count density, and not on edge detection, is used to measure LVEF. SPET myocardial perfusion images, gated in eight time bins, were recorded in 50 patients 60 min after the injection of 925 MBq technetium-99m tetrofosmin. Masking of non-myocardial structures and thresholding resulted in images in which only myocardial walls had significant non-zero values. The distance of the wall relative to the centre of the cavity was calculated in the three-dimentional space as the first moment of the count rate distribution along radii originating in the centre of the cavity. LVEF was calculated using, for each time bin, the sum of the cube of all distances as an estimate of the cavity volume. The method required minimal operator interventions and was successful in all patients, including those with severe perfusion defects. Intraobserver and interobserver variability was excellent, with regression coefficients of 0.97 and standard deviations of 4.5% and 4.7%, respectively. For 30 patients, the measurements were validated against planar equilibrium radionuclide angiography (ERNA) that was obtained within an interval of 1 week. LVEF ranged from 12% to 88%. Agreement between the two methods was excellent (LVEFERNA=1.05+0.92 LVEFGSPET, r=0.93, P=0.023, SEE=7.06). The Bland-Altman analysis did not show any apparent trend in the differences between ERNA and gated SPET over a wide range of ejection fractions. The standard deviation of the differences was 3. 1%. In addition no relationship was found between the two methods and the severity of perfusion defects. In conclusion, accurate measurements of LVEF are obtained from gated SPET perfusion images using a method based on statistical analysis of the count rate density. This method did not deteriorate even in the presence of severe perfusion defects and could therefore be used in following patients after myocardial infarction.

    View details for Web of Science ID A1996WA39700012

    View details for PubMedID 8929317

  • Treatment of hormone-refractory prostate cancer with Y-90-CYT-356 monoclonal antibody CLINICAL CANCER RESEARCH Deb, N., Goris, M., Trisler, K., Fowler, S., Saal, J., Ning, S. C., Becker, M., Marquez, C., Knox, S. 1996; 2 (8): 1289-1297

    Abstract

    A Phase I dose-escalation study using 90Y-CYT-356 monoclonal antibody was performed in 12 patients with hormone-refractory prostate carcinoma. Biodistribution studies using 111In-CYT-356 were performed 1 week before 90Y-CYT-356 administration. Of the 12 patients, 58% had at least one site of disease imaged after administration of 111In-CYT-356. The dose of 90Y ranged from 1.83-12 mCi/m2. Both 111In and 90Y-CYT-356 were tolerated well, without significant nonhematological toxicity. Myelosuppression was the dose-limiting toxicity and occurred at dose levels of 4.5-12 mCi/m2. Of the patients receiving

    View details for Web of Science ID A1996VB19900006

    View details for PubMedID 9816299

  • Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma CLINICAL CANCER RESEARCH Knox, S. J., Goris, M. L., Trisler, K., Negrin, R., Davis, T., Liles, T. M., GRILLOLOPEZ, A., Chinn, P., Varns, C., Ning, S. C., Fowler, S., Deb, N., Becker, M., Marquez, C., Levy, R. 1996; 2 (3): 457-470

    Abstract

    A Phase I/II dose escalation study of 90Y-murine anti-CD20 monoclonal antibody (mAb) in patients with recurrent B-cell lymphoma was performed. The primary objectives of the study were: (a) to determine the effect of the preinfusion of unlabeled anti-CD20 mAb on the biodistribution of 111In-anti-CD20 mAb; (b) to determine the maximal tolerated dose of 90Y-anti-CD20 mAb that does not require bone marrow transplantation; and (c) to evaluate the safety and antitumor effect of 90Y-anti-CD20 mAb in patients with recurrent B-cell lymphoma. Eighteen patients with relapsed low- or intermediate-grade non-Hodgkin's lymphoma were treated. Biodistribution studies with 111In-anti-CD20 mAb were performed prior to therapy. Groups of three or four patients were treated at dose levels of approximately 13.5, 20, 30, 40, and 50 mCi 90Y-anti-CD20 mAb. Three patients were retreated at the 40-mCi dose level. The use of unlabeled antibody affected the biodistribution favorably. Nonhematological toxicity was minimal. The only significant toxicity was myelosuppression. The overall response rate following a single dose of 90Y-anti-CD20 mAb therapy was 72%, with six complete responses and seven partial responses and freedom from progression of 3-29+ months following treatment. Radioimmunotherapy with

    View details for Web of Science ID A1996TY62000004

    View details for PubMedID 9816191

  • Automatic registration and alignment on a template of cardiac stress & rest SPECT images IEEE Workshop on Mathematical Methods in Biomedical Image Analysis (MMBIA) Declerck, J., Feldmar, J., Betting, F., Goris, M. L. I E E E, COMPUTER SOC PRESS. 1996: 212–221
  • (90)Yttrium labeled anti-CD20 therapy for recurrent B cell lymphoma Davis, T. A., Goris, M. L., Trisler, K. D., Negrin, R., Liles, T. M., Fowler, S. F., Deb, N., Becker, M., Marquez, C. M., Ning, S., Levy, R., Knox, S. AMER SOC HEMATOLOGY. 1995: 1080–80
  • MYOCARDIAL PERFUSION IMAGING WITH TC-99M TETROFOSMIN - COMPARISON TO (TL)-T-201 IMAGING AND CORONARY ANGIOGRAPHY IN A PHASE-III MULTICENTER CIRCULATION Zaret, B. L., RIGO, P., Wackers, F. J., Hendel, R. C., Braat, S. H., Iskandrian, A. S., SRIDHARA, B. S., Jain, D., Itti, R., Serafini, A. N., Goris, M. L., Lahiri, A., Halders, S., KOPPEJANS, L., CAJOB, I., Willems, P., Bontemps, L., EGROIZARD, P., Sayegh, Y., Fraysse, M., BENOIT, T. R., LELLERLO, B., Foulon, J., Kline, R., MORRISSETTE, G., Price, L., Jackson, R., Spies, S., Bellow, S., Leonard, S., Bull, C., Sridhara, B., Raval, U., Crawley, J., Smith, T., Iskandrian, A., Heo, J., UNTEEKER, W., FEINSMITH, N., Cave, V., WASSERLEBEN, V., McDougall, R., Blake, L., Gurevich, N., Fujii, C., Ezuddin, S., Sequeira, R., Lowery, M., Wackers, F. J., Mattera, J., McMahon, M., Saari, M. 1995; 91 (2): 313-319
  • DOSIMETRY COMPUTATION FROM TISSUE DISTRIBUTION DATA ENTERED IN AN ELECTRONIC MOUSE MODEL WITH CONVOLUTION OF THE BETA-RAY DEPOSITION PROFILE Goris, M. L., Nielsen, K. K., NAPEL, S. A. SOC NUCLEAR MEDICINE INC. 1994: P161–P161
  • ORGAN MODELING IN THE QUANTITATION OF PLANAR IMAGES FOR DISTRIBUTION STUDIES 9th Conference on Radioimmunodetection and Radioimmunotherapy of Cancer Goris, M. L., Knox, S. A., Nielsen, K. R., BOUILLANT, O. JOHN WILEY & SONS INC. 1994: 919–22

    Abstract

    The advantage of whole-body imaging for distribution studies is that it accounts for all activities. The problem, however, is that the classic approach to determining distribution from planar images does not accommodate overlapping structures. That approach assumes implicitly that the sampling region is a prismoid whose cross-section, parallel to the detector plane, is defined by a region of interest and whose sides are orthogonal to the detector plane.In the proposed organ-model approach, the region of interest is assumed explicitly to be the projected shadow of an organ or structure, whose general shape is known from anatomic generality, and whose size or specific shape variation is defined by the shadow or region of interest. If "j" is a pixel in the organ shadow "i", a fraction "Vij" of the volume of organ "i" is assumed to project orthogonally in "j". More than one organ shadow can overlap, in which case the volumes projecting in "j" are the sum of "Vij" over "i". The activity "Aj" (count rate density) in any location "j" is defined by the linear combination of volumes "Vij" and concentrations "Ci". For all the pixels in the image, this defines an overdetermined set of linear equations that can be solved by matrix inversion for "Ci", the organ concentrations.The organ-model method was tested on simulated and phantom data. It proved, on serial and repeat processing, to be robust (not subject to large errors due to small variations) if the images had sufficient contrast. This method was found to be superior to the classic approach in evaluating the same data, because in the classic approach, the border regions are too heavily weighted, and therefore, the size of the sampling region is critical. Furthermore, the expression of the results in concentrations is more relevant to dosimetry, the derivation of which is based on cumulative concentrations.Modeling organ shadows is a viable improvement on the use of regions of interest to quantify tracer distribution in planar imaging.

    View details for Web of Science ID A1994MV41800025

    View details for PubMedID 8306280

  • THE HYPOXIC CYTOTOXIN SR-4233 INCREASES THE EFFECTIVENESS OF RADIOIMMUNOTHERAPY IN MICE WITH HUMAN NON-HODGKINS-LYMPHOMA XENOGRAFTS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Wilder, R. B., McGann, J. K., SUTHERLAND, W. R., Waller, E. K., Minchinton, A. I., Goris, M. L., Knox, S. J. 1994; 28 (1): 119-126

    Abstract

    To determine if either the hypoxic cell radiosensitizer etanidazole (SR 2508) or the hypoxic cytotoxin SR 4233 could improve the effectiveness of radioimmunotherapy.LC4 (an IgG1 monoclonal antibody directed toward malignant T cells) and MB-1 (an irrelevant isotype-matched control antibody) were injected intraperitoneally into severe combined immunodeficient phenotype mice with human cutaneous T cell lymphoma xenografts in order to determine the distribution of the antibodies in the tumors and normal tissues as a function of time. Computerized-pO2-histography was used to measure the median oxygen tension in the tumors. Tumor-bearing mice were treated with: (a) LC4; (b) 90Y-LC4; (c) 90Y-MB-1; (d) whole body irradiation delivered via an external 137Cs source; (e) etanidazole and 90Y-LC4; (f) SR 4233 and 90Y-LC4; (g) etanidazole; and (h) SR 4233. An additional group of mice received no treatment and served as controls. A tumor growth delay assay was used to assess the effectiveness of the different treatment regimens.LC4 accumulated in the tumors to a significantly greater extent than MB-1 (p < 0.001) and reached a peak concentration in the tumors 5 days post-injection. The human cutaneous T cell lymphoma xenografts had a relatively low median oxygen tension. LC4 by itself was able to produce a minor decrease in tumor size (control vs. LC4; p = 0.001). 90Y-LC4 produced greater tumor growth delay than LC4 alone (LC4 vs. 90Y-LC4; p = 0.01); however, the Yttrium-90 caused neutropenia and weight loss. The 90Y-labeled tumor-specific and non-specific antibodies both exerted greater tumor growth delay than externally delivered whole body irradiation (p < or = 0.03) due to preferential uptake of the antibodies in the tumors. Etanidazole and SR 4233 by themselves did not significantly inhibit the growth of the tumors. Etanidazole did not significantly enhance the tumor growth delay produced by 90Y-LC4 (90Y-LC4 vs etanidazole and 90Y-LC4, p = 0.13). SR 4233, on the other hand, did enhance the tumor growth delay produced by 90Y-LC4 (90Y-LC4 vs. SR 4233 and 90Y-LC4, p = 0.046). The neutropenia and weight loss caused by 90Y-LC4 were exacerbated slightly (< 10%) by the administration of SR 4233.A first generation hypoxic cytotoxin, SR 4233, was able to enhance the tumor growth delay produced by radioimmunotherapy in severe combined immunodeficient phenotype mice with human cutaneous T cell lymphoma xenografts.

    View details for Web of Science ID A1994MP35300016

    View details for PubMedID 8270432

  • MODELING THE INTEGRATION OF MYOCARDIAL REGIONAL PERFUSION AND FUNCTION NUCLEAR MEDICINE COMMUNICATIONS Goris, M. L., Thompson, C., Malone, L. J., Franken, P. R. 1994; 15 (1): 9-20

    Abstract

    The purpose of the study is to describe a method for the investigation of myocardial kinetics (wall motion or wall thickening) to define myocardial perfusion characteristics further. The data are myocardial perfusion single photon emission computed tomographic images gated in eight time bins, following the administration of a 99Tcm-labelled perfusion agent. Wall motion is defined by the phase and amplitude of the centripetal motion of the first moment of the myocardial count rate density distribution along a radius originating in the centre of the left ventricular cavity. Wall thickening is defined by phase and amplitude of the changes in the second moment of the density distribution along the radius multiplied by the maximum density. Wall motion amplitude was abnormal in 28% of transient and 43% of fixed perfusion abnormalities, phase delays were present in 28 and 57%, respectively. Wall thickening was abnormal in amplitude in 14% of transient and 86% of fixed perfusion abnormalities. We conclude that the positive predictive value of wall-thickening abnormalities relative to fixed perfusion abnormalities is high (86%). Whether fixed perfusion defects with normal wall thickening represent viable myocardium remains to be investigated.

    View details for Web of Science ID A1994MZ73100003

    View details for PubMedID 8152699

  • DETERMINANTS OF LOW-DOSE RATE EFFECTS ASSOCIATED WITH RADIOIMMUNOTHERAPY ANTIBODY IMMUNOCONJUGATES AND RADIOPHARMACEUTICALS Knox, S. J., Sutherland, W., Goris, M. L. 1993; 6 (3): 197-207
  • LOCAL HYPERTHERMIA AND SR-4233 ENHANCE THE ANTITUMOR EFFECTS OF RADIOIMMUNOTHERAPY IN NUDE-MICE WITH HUMAN COLONIC ADENOCARCINOMA XENOGRAFTS CANCER RESEARCH Wilder, R. B., Langmuir, V. K., Mendonca, H. L., Goris, M. L., Knox, S. J. 1993; 53 (13): 3022-3027

    Abstract

    Local hyperthermia and the hypoxic cytotoxin SR 4233 were administered to nude mice with 693 +/- 47 mm3 (mean +/- SE) s.c. HCT-8 human colonic adenocarcinoma xenografts in an attempt to enhance the antitumor effects of radioimmunotherapy. Biodistribution studies revealed preferential binding of NR-Lu-10, a murine monoclonal antibody, to the tumors compared with an isotype-matched control antibody, CCOO16-3.A single injection of 25 microCi 90Y-NR-Lu-10 significantly inhibited tumor growth (control versus 90Y-NR-Lu-10: P = 0.048). The administration of hyperthermia at 41.5 degrees C for 1 h immediately following the injection of 111In-labeled NR-Lu-10 up-regulated tumor-associated antigen expression and increased antibody uptake in the tumors by 73% (P = 0.001) without significantly affecting antibody uptake in normal tissues. However, the heat treatment did not produce a more homogeneous distribution of the antibodies in the tumors and did not significantly enhance the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.07). The administration of local hyperthermia at 43.0 degrees C for 1 h, on the other hand, had direct cytotoxic effects (P = 0.03) and enhanced the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.01). SR 4233 also enhanced the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.03). The greatest antitumor effects were observed when both hyperthermia at 43.0 degrees C and SR 4233 were administered in combination with 90Y-NR-Lu-10 (P = 0.002). No toxicity was produced by the local hyperthermia, and the only toxicities produced by 90Y-NR-Lu-10 and SR 4233 were neutropenia and weight loss.

    View details for Web of Science ID A1993LL13100018

    View details for PubMedID 8319209

  • CORRELATION OF TUMOR SENSITIVITY TO LOW-DOSE-RATE IRRADIATION WITH G2/M-PHASE BLOCK AND OTHER RADIOBIOLOGICAL PARAMETERS RADIATION RESEARCH Knox, S. J., Sutherland, W., Goris, M. L. 1993; 135 (1): 24-31

    Abstract

    The efficacy of exponentially decreasing low-dose-rate irradiation was compared with that of equivalent doses of multiply fractionated high-dose-rate external-beam irradiation in mice with three different kinds of tumors that varied in terms of alpha/beta ratio, tumor volume doubling times, and cell cycle times. Cell cycle distribution was measured after low-dose-rate and high-dose-rate irradiation. The relative efficacy of low-dose-rate irradiation versus equivalent doses of high-dose-rate irradiation was correlated with the extent of arrest of cells in G2 phase of the cell cycle. Unlike 38C13 murine B-cell lymphoma, neither the HT29 human colorectal xenograft or the SNB75 human glioblastoma xenograft was significantly more sensitive to low-dose-rate than fractionated high-dose-rate irradiation. The 38C13 B-cell lymphoma also had the shortest tumor volume doubling and cell cycle times, the most G2 arrest after low-dose-rate irradiation, more G2 arrest with low-dose-rate than high-dose-rate irradiation, and the highest alpha/beta ratio. The data presented here support the hypothesis that dose-rate effects may be minimal for tumors with small shoulders and large alpha/beta ratios and that arrest of cells in G2 phase plays an important role in cell death mediated by low-dose-rate irradiation. The proliferative rates of tumor cells may modify dose-rate effects further, and the interaction of all of these factors may explain in part the increased efficacy of low-dose-rate irradiation and radioimmunotherapy compared with high-dose-rate irradiation that has been reported in some animal models.

    View details for Web of Science ID A1993LM85600003

    View details for PubMedID 8327657

  • THE EFFECT OF UNLABELED MONOCLONAL-ANTIBODY (MAB) ON THE BIODISTRIBUTION OF I-131 ANTIIDIOTYPE MAB IN MURINE B-CELL LYMPHOMA RADIOTHERAPY AND ONCOLOGY Schiele, J., Knox, S. J., RUEHL, W., Goris, M. L. 1992; 24 (3): 169-176

    Abstract

    The 38C13 murine B cell lymphoma model was used to study the effect of the preinjection of unlabelled anti-idiotype monoclonal antibody (mAb) on the subsequent biodistribution of 131I-anti-idiotype mAb. Mice with established tumors received 0-500 micrograms of unlabelled anti-idiotype mAb 24 h prior to the administration of 131I-anti-idiotype (specific), or both 125I-anti-idiotype and 131I-isotype-matched irrelevant control (nonspecific) mAb. Mice were counted daily in a gamma counter and sacrificed at 2-144 h following injection. Mice were dissected and the weight and activity of the animals and organs were measured. Mice were bled periodically and circulating idiotype levels were measured using an ELISA assay. Five hundred micrograms of unlabelled anti-idiotype mAb increased the retention time of the specific but not the nonspecific mAb in all organs and tumor. Following pretreatment with unlabelled mAb, the cumulative tumor/whole body and tumor/normal organ ratios became similar to those of the nonspecific mAb, with concentration ratios (specific/nonspecific mAb) of approximately 1, which persisted until 96 h post injection when circulating idiotype reappears in antigen excess. In the absence of unlabelled mAb there was less retention in tumor and normal tissue. This is presumed to be due in part to decreased levels of circulating 131I-mAb secondary to rapid plasma clearance of antigen-antibody complexes and tumor cell mediated dehalogenation, which results when the specific mAb specifically binds the targeted antigen. Thus, the addition of unlabelled mAb increased the retention by decreasing the specific behavior of the anti-idiotypic antibody.

    View details for Web of Science ID A1992JL59000005

    View details for PubMedID 1410571

  • PARATHYROID IMAGING - USE OF DUAL ISOTOPE SCINTIGRAPHY FOR THE LOCALIZATION OF ADENOMAS BEFORE SURGERY CLINICAL NUCLEAR MEDICINE Basso, L. V., Keeling, C., Goris, M. L. 1992; 17 (5): 380-383

    Abstract

    Seventy-nine patients with primary hyperparathyroidism, whose average preoperative blood calcium level was 11.6 mg/dl, underwent thallium-technetium dual isotope scintigraphy of the thyroid and parathyroids. For patients who had surgery, the detection and localization rate of parathyroid disease or the sensitivity was low (0.53), but the positive predictive value for the location was high (0.80). Correct localization correlated positively with the weight of the tumor but not significantly with the parathyroid hormone blood level nor with the blood calcium level. Unprocessed data alone were sufficient to predict correctly the location in two thirds of the detected cases. Computer processing increased the sensitivity without decreasing the specificity. Those results, at variance with earlier published data but congruent with another more recent study, require a reevaluation of the role of this scintigraphic technique in the management of hyperparathyroidal patients.

    View details for Web of Science ID A1992HT61000009

    View details for PubMedID 1316819

  • OVERVIEW OF ANIMAL STUDIES COMPARING RADIOIMMUNOTHERAPY WITH DOSE EQUIVALENT EXTERNAL BEAM IRRADIATION RADIOTHERAPY AND ONCOLOGY Knox, S. J., Goris, M. L., Wessels, B. W. 1992; 23 (2): 111-117

    Abstract

    As the field of radioimmunotherapy (RIT) continues to develop and looks increasingly promising, there is growing interest in the radiobiology of RIT. Recently, several investigators have conducted studies in animal models comparing the relative efficacy of RIT with dose equivalent external beam irradiation. Although these studies are the first of many to follow, the results are provocative and several patterns are suggested by the available data. The results of the studies are summarized and compared, and preliminary hypotheses that might explain the reported observations are discussed. In summary, results from studies comparing the efficacy of RIT with external beam irradiation have been variable and may be indicative of different underlying mechanisms. While the particular experimental model, design and methodology used to compare the efficacy of RIT with external beam irradiation are probably important influences upon subsequent observations, it appears that for a given tumor type, the size of the survival curve shoulder or alpha/beta ratio, and tumor doubling time are important determinants of the magnitude of the dose rate effect. When this effect is minimal, it is possible that other factors such as reoxygenation, the arrest of cells in G2, and selective targeting of tumor by radiolabelled antibody may explain, in part, the increased efficacy of RIT compared with external beam irradiation that has been observed in some systems.

    View details for Web of Science ID A1992HJ27900007

    View details for PubMedID 1546186

  • Case report: diffuse gastrointestinal bleeding. American journal of physiologic imaging Goris, M. L., Licho, R. 1992; 7 (1): 42-43

    Abstract

    Diffuse gastrointestinal bleeding in an immunodeficient patient is presented. Two hours after in vivo erythrocyte labeling, abnormal activity was observed in the wall of a distended colon. If this abnormal concentration had been luminal, a focal, surgically treatable lesion could not have been excluded. This pattern of hemorrhagic colonic lesions has been described pathologically, but not scintigraphically, in immune deficient patients.

    View details for PubMedID 1325815

  • THE BIODISTRIBUTION OF IN-111 ANTI-BFGF IN A VARIETY OF TUMORS - CORRELATION WITH CELL-BINDING ASSAYS ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Knox, S. J., Brown, J. M., McGann, J., Sutherland, W., Goris, M. L., Herblin, W. F., Gross, J. L. 1991; 638: 497-502

    View details for Web of Science ID A1991JM20900072

    View details for PubMedID 1785829

  • LONG-TERM SCINTIGRAPHIC APPEARANCE OF EXTREMITIES FOLLOWING BONE-TUMOR RESECTION AND ALLOGRAFT RECONSTRUCTION CLINICAL NUCLEAR MEDICINE SMITH, J. T., Smith, L. M., Rinsky, L., Goris, M. L. 1991; 16 (12): 907-909

    Abstract

    The authors retrospectively reviewed the Tc-99m medronate scan findings in six patients who had no evidence of metastatic disease following en bloc resection of a primary osteosarcoma and subsequent limb reconstruction using allograft bone. Persistently increased radionuclide uptake was noted at the junction between the host bone and the graft, while the graft cortical bone showed persistently decreased activity. Radionuclide uptake at the periphery of the graft varied. Over time the youngest patient in the series had increasingly normal scan findings.

    View details for Web of Science ID A1991KC60900005

    View details for PubMedID 1663013

  • PARATHYROID IMAGING JOURNAL OF NUCLEAR MEDICINE Goris, M. L., Basso, L. V., Keeling, C. 1991; 32 (5): 887-889

    View details for Web of Science ID A1991FL18300037

    View details for PubMedID 1827150

  • NONINVASIVE DIAGNOSIS OF TRANSPLANT CORONARY-ARTERY DISEASE BY TC-99M ISONITRILE SCINTIGRAPHY Lucas, J. R., Valantine, H. A., Hunt, S., FUJIK, C. Y., Goris, M. L., Schroeder, J. S. SLACK INC. 1991: A233–A233
  • THE QUANTIFICATION OF PLANAR SCINTIGRAPHY USING 3-DIMENSIONAL MODELING OF ORGAN SHADOWS 11TH INTERNATIONAL CONF ON INFORMATION PROCESSING IN MEDICAL IMAGING Goris, M. L. WILEY-LISS, INC. 1991: 531–539

    Abstract

    A method to define biodistribution from planar scintigraphic data is presented. Sampling regions or regions of interest (ROI's) are first defined as the projection contour of organs. From anatomical knowledge the three dimensional volume of the organ whose shadow has been traced is reconstructed. When the relevant organ volumes including the whole body or relevant whole body part have been defined, the count rate density in each pixel is assumed to represent the sum of the product of the projecting organ partial volumes times the tracer concentrations in the underlying organs. The solution (the definition of organ concentrations) is found by a matrix inversion. Validation is obtained in two ways. The first method is illustrative: an image is reconstructed from the defined volumes modulated by the computed concentrations. This image, if the method is correct, should be a crisp equivalent of the original data and closely similar to it following blurring with a convolution kernel equal to the imaging system's point spread function. The second is analytical: from reconstructed S.P.E.C.T. data in which voxel values are directly proportional to organ concentrations, a planar image is reconstructed. Organ average voxel values are computed in the S.P.E.C.T. image with volumetric ROI's and in the reprojected planar image using the method described here. The methods should yield the same concentration data but for a scaling factor. The method has the advantage that it yields volumetric and concentration data which are directly applicable to MIRD type analysis. In effect, the standard man assumptions in MIRD analysis have been incorporated in the calculation of the concentrations.

    View details for Web of Science ID A1991BS33M00038

    View details for PubMedID 1988999

  • THE BIODISTRIBUTION OF IN-111 ANTI-BFGF IN A VARIETY OF TUMORS - CORRELATION WITH CELL-BINDING ASSAYS CONF ON THE FIBROBLAST GROWTH FACTOR FAMILY Knox, S. J., Brown, J. M., McGann, J., Sutherland, W., Goris, M. L., Herblin, W. F., Gross, J. L. NEW YORK ACAD SCIENCES. 1991: 497–502
  • DETERMINANTS OF THE ANTITUMOR EFFECT OF RADIOLABELED MONOCLONAL-ANTIBODIES CANCER RESEARCH Knox, S. J., Levy, R., MILLER, R. A., UHLAND, W., Schiele, J., RUEHL, W., FINSTON, R., DAYLOLLINI, P., Goris, M. L. 1990; 50 (16): 4935-4940

    Abstract

    The murine B-cell lymphoma 38C13 model was used to study the radiobiological effect of 131I-monoclonal antibody (MAB) therapy compared with dose equivalent external beam irradiation. Continuous exponentially decreasing low dose rate (LDR) gamma-irradiation, and multiply fractionated (MF) X-irradiation were compared with dose equivalent 131I-MAB. The relative therapeutic efficacy of radioimmunotherapy, and the relative contribution of (a) low dose rate; (b) whole body irradiation; and (c) microdosimetry to the overall effect were determined. Groups of mice with or without B-cell lymphoma were treated with either (a) 131I-anti-idiotype MAB; (b) 131I-isotype-matched irrelevant control MAB; (c) 5-15 Gy 250 kV X-irradiation given as a single fraction; (d) 2.5-30 Gy 250 kV X-irradiation given in 10 fractions/2 weeks; or by (e) continuous exponentially decreasing gamma-irradiation via a 137Cs source, which simulated the effective t1/2 of the 131I-MAB. In tumor-free mice the LD50/30 was approximately 10 Gy for MF and LDR external irradiation, and 11-12 Gy for 131I-MAB. However, the effect of these modes of irradiation on tumor size differed significantly. The cumulative percentage of tumor reduction averaged over 12 days was 0.635 +/- 0.055%/Gy for MF, and 1.36 +/- 0.061%/Gy for LDR external irradiation (a relative efficacy factor of 1.63 for LDR irradiation; P = 0.01). Assuming homogeneous body distribution, the tumor reduction effect over 12 days for 131I-MAB was 2.064 +/- 0.133%/Gy for specific, and 1.742 +/- 0.1%/Gy for nonspecific isotype-matched irrelevant 131I-MAB (P = 0.02). When 131I-MAB was compared to LDR external irradiation, the relative efficacy factor was 1.99 (P less than 0.001). In summary, there was a dose rate effect on tumor response, which may in part explain the efficacy of radioimmunotherapy. The additional effect of 131I-MAB on tumor response was only partially explained by the cumulative concentration ratio of 131I-MAB tumor/131I-MAB whole body, which was on average 1.7. This relatively low concentration ratio was partly due to tumor-mediated dehalogenation. Thus, the overall tumor response was a function of the total dose, dose rate, and both the specific and nonspecific distribution of 131I-MAB.

    View details for Web of Science ID A1990DT62000020

    View details for PubMedID 2379158

  • Validation of diagnostic procedures on stratified populations: application on the quantification of thallium myocardial perfusion scintigraphy. American journal of physiologic imaging Goris, M. L., BRETILLE, J., Askienazy, S., Purcell, G. P., Savelli, V. 1989; 4 (1): 11-15

    Abstract

    In this report we present a method for the quantitative description of the degree of deviation from the norm of 201thallium single photon emission tomographic (SPECT) data. Validation is obtained from the frequency of "positive" outcomes in subgroup of patients in whom the prevalence of coronary artery disease, for the group as a whole, is known, even if individual patient outcomes are not verified. This approach overcomes the bias associated with nonrandomized clinical studies, in which the likelihood that a more invasive but definitive procedure (coronary arteriogram) will be performed is influenced by the result of the outcome of the procedure under study.

    View details for PubMedID 2647110

  • NONINVASIVE ASSESSMENT OF DONOR AND NATIVE HEART FUNCTION AFTER HETEROTOPIC HEART-TRANSPLANTATION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Allen, M. D., NAASZ, C. A., Popp, R. L., Hunt, S. A., Goris, M. L., Oyer, P. E., Stinson, E. B. 1988; 95 (1): 75-81

    Abstract

    The contribution of the donor heart to total circulatory performance after heterotopic heart transplantation has been difficult to assess. First-pass nuclear angiocardiography and directional Doppler echocardiography were used to examine separately left and right ventricular function of the donor heart after heterotopic transplantation. A comparison was made between two patients, one with a low initial pulmonary vascular resistance and one with a high, relatively fixed pulmonary vascular resistance. In both cases, currently available noninvasive techniques allowed confirmation of the expectation that the donor left ventricle can function effectively as a left ventricular bypass. In neither case was recovery of the native heart demonstrated. The contribution of the donor right ventricle to total right ventricular output appeared to be dependent on the condition of the donor heart and on the pulmonary vascular resistance. In situations with a high pulmonary vascular resistance and end-stage right ventricular failure, it was concluded that the donor heart may not at first constitute an effective assist for the native right ventricle. Native right ventricular failure may then become a major factor influencing survival after heterotopic heart transplantation.

    View details for Web of Science ID A1988L686700010

    View details for PubMedID 3275840

  • Two-dimensional mapping of three-dimensional SPECT data: a preliminary step to the quantitation of thallium myocardial perfusion single photon emission tomography. American journal of physiologic imaging Goris, M. L., Boudier, S., BRIANDET, P. A. 1987; 2 (4): 176-180

    Abstract

    A method is presented by which tomographic myocardial perfusion data are prepared for quantitative analysis. The method is characterized by an interrogation of the original data, which results in a size and shape normalization. The method is analogous to the circumferential profile methods used in planar scintigraphy but requires a polar-to-cartesian transformation from three to two dimensions. As was the case in the planar situation, centering and reorientation are explicit. The degree of data reduction is evaluated by reconstructing "idealized" three-dimensional data from the two-dimensional sampling vectors. The method differs from previously described approaches by the absence in the resulting vector of a coordinate reflecting cartesian coordinate in the original data (slice number).

    View details for PubMedID 3502531

  • Interrogation and display of single photon emission tomography data as inherently volume data. American journal of physiologic imaging Goris, M. L., Boudier, S., BRIANDET, P. A. 1986; 1 (4): 168-180

    Abstract

    The purpose of single photon emission computed tomography (SPECT) data is to map the tracer concentration from the three-dimensional object into a three-dimensional image array. The conventional interrogation of the data is through slice interrogation. In this paper we explore display methods in which the data are directly interrogated and processed as three-dimensional data. This includes direct addressing of sagittal, transverse, and frontal slices, around a targeted subvolume, and direct addressing of nonorthogonal slices. The three-dimensional aspect of the data is further accommodated by thresholding and edge definition in space. Finally, morphological information, which is sparse in scintigraphic slices, is recaptured by the generation of planar data derived from data processed in the three-dimensional space.

    View details for PubMedID 3502525

  • SKELETAL SCINTIGRAPHY FOR THE DIAGNOSIS OF MALIGNANT METASTATIC DISEASE TO THE BONES RADIOTHERAPY AND ONCOLOGY Goris, M. L., BRETILLE, J. 1985; 3 (4): 319-329

    Abstract

    The use of skeletal scintigraphy for the detection of metastatic disease of the bone is reviewed. The review is based on published data for sensitivity, specificity, yield and prognostic value. The analysis, and interpretation of published data is complicated by the variation in criteria. It appears nonetheless, that for a number of tumors the relative (in comparison with other methods) and absolute (based on outcome prediction) sensitivity is high. For certain tumors in early stages, and in asymptomatic patients the yield (of positive studies) is low, even when the prognostic value is high. Those factors should be weighed with the availability of therapeutic options to determine the clinical efficacy of skeletal scintigraphy.

    View details for Web of Science ID A1985AKR4700005

    View details for PubMedID 3892595

  • A STOCHASTIC INTERPRETATION OF THALLIUM MYOCARDIAL PERFUSION SCINTIGRAPHY INVESTIGATIVE RADIOLOGY Goris, M. L., Gordon, E., Kim, D. 1985; 20 (3): 253-259

    Abstract

    A method is presented for the quantitative interpretation of thallium-201 myocardial perfusion studies. The data are planar images collected immediately following the stress injection, and 4 to 6 hours later. Data analysis consists of preprocessing, including thresholding of the original data, and data reduction using a variant of the circumferential profile methods. The profiles are subdivided into segments, and for each segment the difference between the norm and the actual data is computed. This difference is a quantitative symptom, whose size is assumed to be related to the probability of having the disease. The relationship between the size of the symptom in each of nine segments (three segments/view in three views) and the probability of disease is expressed in a table in which for 30 diseases (combinations of vascular lesions) the sensitivity for each of the nine symptoms is described as a Gaussian function whose average and standard deviation are computed from previous validated cases. Using an arbitrary prevalence, the post-testing probability can then be computed using Bayes' formula sequentially. The sensitivities, however, are not expressed as a binary function of the presence or absence of a symptom, but as a distribution function defined by experience. The method is sensitive for the detection of isolated left anterior descending disease (100%) and triple vessel disease (96%). When specific combinations of vascular lesions are recognized the specificity increases from 79% (when unspecified abnormalities are recognized) to 87% when left anterior descending disease or triple vessel disease is recognized.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1985AJF7100005

    View details for PubMedID 4030262

  • DILTIAZEM AND PROPRANOLOL, ALONE AND IN COMBINATION, ON EXERCISE PERFORMANCE AND LEFT-VENTRICULAR FUNCTION IN PATIENTS WITH STABLE EFFORT ANGINA - A DOUBLE-BLIND, RANDOMIZED, AND PLACEBO-CONTROLLED STUDY ACTA PHARMACOLOGICA ET TOXICOLOGICA Schroeder, J. S., Hung, J., LAMB, I. H., Connolly, S. J., Jutzy, K. R., Goris, M. L. 1985; 57: 55-60

    Abstract

    Diltiazem and propranolol alone and in combination as antianginal agents were compared with placebo in 12 patients with stable exertional angina at Stanford University Medical Center. The patients performed symptom-limited, multi-stage upright bicycle ergometric exercise while undergoing radionuclide angiographic studies every two weeks while being treated with 90 mg of diltiazem four times daily, 60 mg of propranolol four times daily, a combination of 90 mg of diltiazem and 60 mg of propranolol four times daily, and placebo. Diltiazem, propranolol and a combination all significantly increased exercise duration compared to placebo (526 +/- 149, 525 +/- 115, and 549 +/- 129 vs 430 +/- 132 sec.). Although rate pressure product and heart rate decreased with diltiazem therapy at submaximal workloads, these values were unchanged at peak exercise in contrast to propranolol or the combination of propranolol or diltiazem. Diltiazem decreased the sub-maximal and maximal degree of exercise-induced ST segment depression by over 50% compared to placebo (P less than 0.01 vs placebo). Diltiazem resulted in a higher exercise left ventricular ejection fraction compared to placebo, propranolol or the combination of diltiazem or propranolol (all less than P less than 0.05). Sinus bradycardia or orthostatic hypertension occurred in four patients on the high-dose combination therapy and required dose reduction. We concluded that high-dose diltiazem, appeared to be even more effective than moderate-dose propranolol or the combination of diltiazem and propranolol in improving exercise tolerance, electrocardiographic evidence of myocardial ischaemia and left ventricular function in patients with stable effort angina due to occlusive coronary artery disease.

    View details for Web of Science ID A1985ARG3800008

    View details for PubMedID 4061105

  • RELATIVE PROGNOSTIC VALUE OF 4 COMPETING TESTS ONE MONTH AFTER UNCOMPLICATED MYOCARDIAL-INFARCTION Dennis, C. A., Hung, J., Kraemer, H., Goris, M. L., Barnes, D., DeBusk, R. F. ELSEVIER SCIENCE INC. 1984: 534–34
  • COMPARATIVE VALUE OF MAXIMAL TREADMILL TESTING, EXERCISE THALLIUM MYOCARDIAL PERFUSION SCINTIGRAPHY AND EXERCISE RADIONUCLIDE VENTRICULOGRAPHY FOR DISTINGUISHING HIGH-RISK AND LOW-RISK PATIENTS SOON AFTER ACUTE MYOCARDIAL-INFARCTION AMERICAN JOURNAL OF CARDIOLOGY Hung, J., Goris, M. L., Nash, E., Kraemer, H. C., DeBusk, R. F., Berger, W. E., Lew, H. 1984; 53 (9): 1221-1227

    Abstract

    The prognostic value of symptom-limited treadmill exercise electrocardiography, exercise thallium myocardial perfusion scintigraphy and rest and exercise radionuclide ventriculography was compared in 117 men, aged 54 +/- 9 years, tested 3 weeks after a clinically uncomplicated acute myocardial infarction (MI). During a mean follow-up period of 11.6 months, 8 men experienced "hard" medical events (cardiac death, nonfatal ventricular fibrillation or recurrent MI) and 14 were hospitalized for unstable angina pectoris, congestive heart failure or coronary bypass surgery (total of 22 combined events). By multivariate analysis (Cox proportional hazards model), peak treadmill work load and the change in left ventricular ejection fraction (EF) during exercise were significant (p less than 0.01) predictors of hard medical events; these 2 risk factors and recurrent ischemic chest pain in the coronary care unit were also significantly predictive (p less than 0.001) for combined events. A peak treadmill work load of 4 METs or less or a decrease in EF of 5% or more below the value at rest during submaximal effort distinguished 22 high-risk patients (20% of the study population) from 89 low-risk patients. The rate of hard medical events within 12 months was 23% (5 of 22 patients), vs 2% (2 of 89 patients) in the high- and low-risk patient subsets, respectively (p less than 0.001). Thus, in patients who underwent evaluation 3 weeks after a clinically uncomplicated MI, exercise radionuclide ventriculography contributed independent prognostic information to that provided by symptom-limited treadmill testing and was superior to exercise thallium scintigraphy for this purpose.

    View details for Web of Science ID A1984SQ45500003

    View details for PubMedID 6711422

  • CHANGES IN REST AND EXERCISE MYOCARDIAL PERFUSION AND LEFT-VENTRICULAR FUNCTION 3 TO 26 WEEKS AFTER CLINICALLY UNCOMPLICATED ACUTE MYOCARDIAL-INFARCTION - EFFECTS OF EXERCISE TRAINING AMERICAN JOURNAL OF CARDIOLOGY Hung, J., Gordon, E. P., Houston, N., Haskell, W. L., Goris, M. L., DeBusk, R. F. 1984; 54 (8): 943-950

    Abstract

    The effects of exercise training on exercise myocardial perfusion and left ventricular (LV) function in the first 6 months after clinically uncomplicated acute myocardial infarction (AMI) were assessed in 53 consecutive men aged 55 +/- 9 years. Symptom-limited treadmill exercise with thallium myocardial perfusion scintigraphy and symptom-limited upright bicycle ergometry with equilibrium gated radionuclide ventriculography were performed 3, 11 and 26 weeks after AMI by 23 men randomized to training and 30 randomized to no training. Peak cycle capacity increased in both groups between 3 and 26 weeks (p less than 0.01), but reached higher levels in trained than in untrained patients (803 +/- 149 vs 648 +/- 182 kg-m/min, p less than 0.01). Reversible thallium perfusion defects were significantly more frequent at 3 than at 26 weeks: 59% and 36% of patients, respectively (p less than 0.05), without significant inter-group differences. Values of LV ejection fraction at rest, submaximal and peak exercise did not change significantly in either group. The increase in functional capacity, i.e., peak treadmill or bicycle workload, that occurred 3 to 26 weeks after infarction was significantly correlated with the increase in peak exercise heart rate (p less than 0.001), but not with changes in myocardial perfusion or LV function determined by radionuclide techniques. Changes in myocardial perfusion or LV function do not appear to account for the improvement in peak functional capacity that occurs within the first 6 months after clinically uncomplicated AMI.

    View details for Web of Science ID A1984TQ43000001

    View details for PubMedID 6496357

  • MECHANISMS FOR DECREASED EXERCISE CAPACITY AFTER BED REST IN NORMAL MIDDLE-AGED MEN AMERICAN JOURNAL OF CARDIOLOGY Hung, J., Goldwater, D., Convertino, V. A., McKillop, J. H., Goris, M. L., DeBusk, R. F. 1983; 51 (2): 344-348

    Abstract

    The mechanisms responsible for the decrease in exercise capacity after bed rest were assessed in 12 apparently healthy men aged 50 +/- 4 years who underwent equilibrium gated blood pool scintigraphy during supine and upright multistage bicycle ergometry before and after 10 days of bed rest. After bed rest, echocardiographically measured supine resting left ventricular end-diastolic volume decreased by 16% (p less than 0.05). Peak oxygen uptake during supine effort after bed rest was diminished by 6% (p = not significant [NS]), whereas peak oxygen uptake during upright effort declined by 15% (p less than 0.05). After bed rest, increases in heart rate were also greater during exercise in the upright than in the supine position (p less than 0.05). Values of left ventricular ejection fraction increased normally during both supine and upright effort after bed rest and were higher than corresponding values before bed rest (p less than 0.05). After bed rest, increased left ventricular ejection fraction and heart rate largely compensated for the reduced cardiac volume during supine effort, but these mechanisms were insufficient to maintain oxygen transport capacity at levels during upright effort before bed rest. These results indicate that orthostatically induced cardiac underfilling, not physical deconditioning or left ventricular dysfunction, is the major cause of reduced effort tolerance after 10 days of bed rest in normal middle-aged men.

    View details for Web of Science ID A1983QA36300023

    View details for PubMedID 6823849

  • SENSITIVITY AND SPECIFICITY OF RADIONUCLIDE EJECTION FRACTIONS IN DOXORUBICIN CARDIOTOXICITY AMERICAN HEART JOURNAL McKillop, J. H., Bristow, M. R., Goris, M. L., Billingham, M. E., BOCKEMUEHL, K. 1983; 106 (5): 1048-1056

    Abstract

    We examined radionuclide-determined left ventricular ejection fractions (LVEF) at rest and during graded exercise in 37 patients receiving doxorubicin (Adriamycin) therapy in whom the risk of developing congestive heart failure (CHF) was precisely defined by endomyocardial biopsy and right heart catheterization. Echocardiographic (Echo %FS) and phonocardiographic (PEP/LVET) measurements of LV function were also determined. An abnormal LVEF at rest (less than or equal to 45%) had a sensitivity of 53% and a specificity of 75% for detecting patients at moderate or high risk of developing CHF. The addition of exercise LVEF increased the sensitivity of detection of moderate or high-risk patients to 89% but lowered the specificity to 41%. Exercise LVEF improved the sensitivity of detection of high-risk patients from 58% to 100%. Echo %FS and PEP/LVET yielded lower sensitivities than rest or exercise LVEF. As a single test, exercise LVEF possesses the sensitivity for use as a screening method for anthracycline cardiotoxicity, but the lack of specificity prevents the use of single values as a definitive test. Single rest LVEF determinations, although more specific than exercise LVEF, do not possess the sensitivity for use as screening or definitive tests.

    View details for Web of Science ID A1983RQ13000013

    View details for PubMedID 6637763

  • THE EFFECT OF DILTIAZEM AND PROPRANOLOL, ALONE AND IN COMBINATION, ON EXERCISE PERFORMANCE AND LEFT-VENTRICULAR FUNCTION IN PATIENTS WITH STABLE EFFORT ANGINA - A DOUBLE-BLIND, RANDOMIZED, AND PLACEBO-CONTROLLED STUDY CIRCULATION Hung, J., LAMB, I. H., Connolly, S. J., Jutzy, K. R., Goris, M. L., Schroeder, J. S. 1983; 68 (3): 560-567

    View details for Web of Science ID A1983RD90200012

    View details for PubMedID 6872168

  • CHANGES IN EXERCISE MYOCARDIAL PERFUSION IN THE 6 MONTHS FOLLOWING MYOCARDIAL-INFARCTION - EFFECTS OF EXERCISE TRAINING Hung, J., Goris, M. L., Gordon, E. P., Houston, N., Haskell, W. L., DeBusk, R. F. ELSEVIER SCIENCE INC. 1983: 662–62
  • THE COMPARATIVE PROGNOSTIC VALUE OF STANDARD TREADMILL TESTING, REST AND EXERCISE THALLIUM MYOCARDIAL PERFUSION SCINTIGRAPHY AND RADIONUCLIDE VENTRICULOGRAPHY 3 WEEKS AFTER MYOCARDIAL-INFARCTION Hung, J., Goris, M. L., Nash, E., Kraemer, H. C., DeBusk, R. F. ELSEVIER SCIENCE INC. 1983: 654–54
  • CARDIOVASCULAR PHYSIOLOGY IN A CASE OF HETEROTOPIC CARDIAC TRANSPLANTATION AMERICAN JOURNAL OF CARDIOLOGY MELVIN, K. R., Pollick, C., Hunt, S. A., McDougall, R., Goris, M. L., Oyer, P., Popp, R. L., Stinson, E. B. 1982; 49 (5): 1301-1307

    Abstract

    Successful heterotopic cardiac transplantation in a 24 year old man with end stage cardiomyopathy provided an opportunity to study cardiovascular physiology. The donor and native hearts, functioning independently in parallel, were studied by serial physical examination, electrocardiography, echocardiography, nuclear angiography and cardiac catheterization. Results indicated that the donor left heart assumed the predominant role in supplying systemic output, possibly contributing to decreasing function of the patient's own (native) heart. Analysis of serial nuclear angiograms revealed an initial postoperative ejection fraction of 52 and 21 percent in the donor and the native left ventricle, respectively; repeat studies 3 months postoperatively showed values of 50 and 9 percent, respectively, indicating significant deterioration in native left ventricular cardiac function. Observation of valve motion of the native heart showed major irregularities of the aortic valve in contrast to seemingly normal, regular mitral valve motion. These data rise interesting questions regarding interpretation of valve motion as an indicator of ventricular function.

    View details for Web of Science ID A1982NH12800029

    View details for PubMedID 7039290

  • CARDIAC STUDIES - THE CLINICAL ASPECTS OF SOFTWARE OPTIONS IEEE TRANSACTIONS ON NUCLEAR SCIENCE Goris, M. L. 1982; 29 (4): 1355-1358
  • EFFECTS OF DILTIAZEM, PROPRANOLOL AND THEIR COMBINATION ON EXERCISE PERFORMANCE AND VENTRICULAR-FUNCTION IN STABLE EFFORT ANGINA - A RANDOMIZED PLACEBO CONTROLLED-STUDY Hung, J., LAMB, I., Connolly, S., Jutzy, K., Goris, M., Hu, M., Schroeder, J. LIPPINCOTT WILLIAMS & WILKINS. 1982: 82–82
  • COMPARATIVE VALUE OF REDISTRIBUTION AND REST THALLIUM STUDIES TO DETECT STRESS-INDUCED MYOCARDIAL ISCHEMIA IN PATIENTS WITH PRIOR INFARCTION Hung, J., Goris, M. L., DeBusk, R. F. EXCERPTA MEDICA INC. 1982: 902–
  • COMPARISON OF CARDIOVASCULAR-RESPONSE TO COMBINED STATIC-DYNAMIC EFFORT, POSTPRANDIAL DYNAMIC EFFORT AND DYNAMIC EFFORT ALONE IN PATIENTS WITH CHRONIC ISCHEMIC-HEART-DISEASE CIRCULATION Hung, J., McKillip, J., Savin, W., Magder, S., Kraus, R., Houston, N., Goris, M., Haskell, W., DeBusk, R. 1982; 65 (7): 1411-1419

    Abstract

    The cardiovascular responses to combined static-dynamic effort, postprandial dynamic effort and dynamic effort alone were evaluated by upright bicycle ergometry during equilibrium-gated blood pool scintigraphy in 24 men, mean age 59 +/- 8 years, with chronic ischemic heart disease. Combined static-dynamic effort and the postprandial state elicited a peak cardiovascular response similar to that of dynamic effort alone; work load 643 +/- 156 and 638 +/- 161 vs 650 +/- 153 kg-m/min, respectively; heart rate 147 +/- 14 and 145 +/- 14 vs 143 +/- 17 beats/min; systolic pressure 195 +/- 26 and 200 +/- 25 vs 197 +/- 25 mm Hg; and rate-pressure product 286 +/- 48 and 292 +/- 55 vs 282 +/- 52. Heart rate, intraarterial systolic and diastolic pressures, rate-pressure product and ejection fraction were similar for the three test conditions at the onset of ischemia and at peak effort. The prevalence and extent of exercise-induced ischemic left ventricular dysfunction, ST-segment depression, angina pectoris and ventricular ectopic activity were also similar during the three test conditions. Direct and indirect measurements of systolic and diastolic blood pressure were highly correlated. The onset of ischemic ST-segment depression and angina pectoris correlated as strongly with heart rate alone as with the rate-pressure product during all three test conditions. The cardiovascular response to combined static-dynamic effort and to postprandial dynamic effort becomes more similar to that of dynamic effort alone as dynamic effort reaches a symptom limit. If significant ischemic and arrhythmic abnormalities are absent during symptom-limited dynamic exercise testing, they are unlikely to appear during combined static-dynamic or postprandial dynamic effort. This simplifies, the task of formulating guidelines for physical effort in patients with chronic ischemic heart disease, especially in providing "clearance" to perform avocational and vocational tasks involving combined static-dynamic and postprandial dynamic effort.

    View details for Web of Science ID A1982NS55500018

    View details for PubMedID 6280892

  • SCINTIGRAPHIC VENTRICULOGRAPHY AND STRESS-TESTING JOURNAL DE BIOPHYSIQUE & MEDECINE NUCLEAIRE Goris, M. L., Hung, J., DeBusk, R. F. 1982; 6 (5): 227-232
  • Krypton-81m ventilation scintigraphy for the diagnosis of pulmonary emboli. Clinical nuclear medicine Goris, M. L., DASPIT, S. G. 1981; 6 (5): 207-212

    Abstract

    The value of ventilation studies in conjunction with pulmonary perfusion scintigraphies for the diagnosis of pulmonary emboli is reviewed. A retrospective study of 273 consecutive cases and comparison with 42 angiographic results provides the data base. The data are compared with previously reported results and confirm the diagnostic gain obtained by ventilation studies. Possible advantages of the use of krypton-81m for the ventilation study are suggested. Finally, with the observed prevalence of six possible scintigraphic outcomes and assuming that two outcomes are diagnostic, it can be shown that the addition of a ventilation study in the diagnostic work-up decreases the average cost of the diagnosis.

    View details for PubMedID 6452981

  • ECG GATING OF TL-201 MYOCARDIAL IMAGES - EFFECT ON DETECTION OF ISCHEMIC-HEART-DISEASE JOURNAL OF NUCLEAR MEDICINE McKillop, J. H., Fawcett, H. D., BAUMERT, J. E., McDougall, I. R., DeBusk, R. F., HARRISON, D. C., Goris, M. L. 1981; 22 (3): 219-225

    Abstract

    Using the angiographic findings as the standard, we have examined the sensitivity and specificity of ECG-gated static thallium-201 myocardial images in 54 patients undergoing selective coronary arteriography. Gated and nongated images, each in anterior, 45 degrees LAO, and 65 degrees LAO projections, were processed by interpolative background subtraction. They were then analyzed separately by four independent observers who were unaware of patient identity, the results of coronary arteriography, and which studies were gated or nongated. No significant differences were observed between the gated and nongated images regarding sensitivity or specificity, the detection rate for reversible myocardial ischemia, the accuracy of prediction of arteriographic extent of disease, or the degree of inter- or intraobserver variability. We conclude that ECG-gated acquisition of T1-201 images does not produce any significant advantages, at least when interpolative background subtraction is used.

    View details for Web of Science ID A1981LF61300004

    View details for PubMedID 7205364

  • THE INDICATIONS FOR AND LIMITATIONS OF BONE-SCINTIGRAPHY IN OSTEOGENIC-SARCOMA - A REVIEW OF 55 PATIENTS CANCER McKillop, J. H., Etcubanas, E., Goris, M. L. 1981; 48 (5): 1133-1138

    Abstract

    The value of radioisotope bone scanning at the time of presentation and serially during follow-up has been evaluated in 55 patients with biopsy-proven osteogenic sarcoma. Many of the patients studied were treated with adjuvant chemotherapy. Bone metastases were detected at presentation in only one patient and in a second patient, proximal extension of the primary tumor not evident on radiographs was demonstrated by the radioisotope technique. During fellow-up, 20 patients experienced bone metastases and each had an abnormal bone scan. Eleven of these patients were asymptomatic for bone metastases at the time the scan became abnormal. Seven patients experienced bone metastases as their first site of tumor recurrence. The detection rate for soft tissue metastases was low, but the scan indicated stump recurrence in three patients. Although the yield is small, bone scanning is justified at presentation be cause the results may profoundly after the management. During follow-up, routine bone cans are indicated in all patients, whether they have symptoms or not.

    View details for Web of Science ID A1981MC74800013

    View details for PubMedID 6268278

  • A FULLY AUTOMATED-DETERMINATION OF THE LEFT-VENTRICULAR REGION OF INTEREST IN NUCLEAR ANGIOCARDIOGRAPHY CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY Goris, M. L., McKillop, J. H., BRIANDET, P. A. 1981; 4 (2): 117-123

    Abstract

    The precise delineation of the left ventricular projection area is an essential part in the quantitative analysis of nuclear angiocardiograms. We have devised an algorithm that permits automation of this step, based on a one-dimensional Laplace operator whose kernel is 2, 2, -2, -4, -2, 2, 2. The operator characteristically enhances "valleys" more than edges and, therefore, favors septal and the valve plane detection. The operator is applied vertically, horizontally, and along both diagonals. Each pass is immediately followed by a local maximum search during which the image resulting from the Laplacian operator is reduced to a binary one, with zeros everywhere except where a local maximum was found along the path of the operator. This resultant image yields a closed "edge" around the left ventricle, even though many structures outside the left ventricle are also delineated. However, the centroid of the ventricle is defined from functional criteria and the region of interest is defined from centroid to first edge. The method has been applied to first-pass and gated studies in anterior and 45 degree left anterior oblique views. In 100 successive cases the ejection fraction obtained automatically was compared to the manual result. The regression equation yielded the relation: automatic method (%) = 1.7 + 1.0 manual method (%) +/-2% (r = 0.995), which is not significantly different from the identity relation. The failure rate was low (13%) but varied from 28% in the first-pass studies in the anterior view, to less than 8% in gated studies in the left ventricular oblique projection.

    View details for Web of Science ID A1981LR74600012

    View details for PubMedID 7249016

  • A THRESHOLDING FOR RADIONUCLIDE ANGIOCARDIOGRAPHY INVESTIGATIVE RADIOLOGY Goris, M. L., BRIANDET, P. A., Thomas, A. J., McKillop, J. H., Sneed, P., WIKLANDER, D. P. 1981; 16 (2): 115-119

    Abstract

    A thresholding algorithm for nuclear angiocardiographic studies is presented. The algorithm is free of operator intervention. The threshold is defined on the basis of the distribution of picture elements with decreasing count rates during systole. The application is valid for first-pass and equilibrium ECG gated studies. Reproducibility by different operators with various degrees of experience is high; concordance of the results with those of contrast studies is within the published ranges. The method provides a reliable step in full automation and standardization of scintigraphic angiocardiographies.

    View details for Web of Science ID A1981LM65600006

    View details for PubMedID 7216701

  • TL-201 MYOCARDIAL IMAGING IN PATIENTS WITH PREVIOUS CARDIAC TRANSPLANTATION CLINICAL RADIOLOGY McKillop, J. H., Goris, M. L. 1981; 32 (4): 447-449

    Abstract

    Thallium-201 myocardial imaging was performed in seven long-term cardiac transplant survivors who were undergoing selective coronary arteriography as a screening test for immune mediated coronary atherosclerosis. The radionuclide studies showed fixed defects in all patients, though none was known to have had a myocardial infarction. Such abnormalities may be due to previous rejection episodes. Reversible ('ischaemic') defects were present in two patients with triple vessel disease, and were also seen in three subjects with minor (less than 50% luminal diameter) stenosis. Ischaemic thallium-201 defects in cardiac transplant recipients indicate the presence of coronary artery disease, though the stenosis may be of a degree which would normally be considered haemodynamically non-significant. The possible role of small vessel disease in producing these defects is discussed.

    View details for Web of Science ID A1981LW86000016

    View details for PubMedID 7018792

  • THE ROLE OF IN-111 LEUKOCYTE SCANNING IN PYODERMA GANGRENOSUM CLINICAL NUCLEAR MEDICINE Johnson, M. A., Wells, J., Frankel, A., Goris, M. L., McDougall, I. R. 1981; 6 (10): 491-494

    View details for Web of Science ID A1981MR09300011

    View details for PubMedID 7296986

  • FAILURE TO DIAGNOSE CARDIAC TRANSPLANT REJECTION WITH TC-99M-PYP IMAGES CLINICAL NUCLEAR MEDICINE McKillop, J. H., McDougall, I. R., Goris, M. L., Mason, J. W., Reitz, B. A. 1981; 6 (8): 375-377

    Abstract

    The possibility of diagnosing transplant rejection using Tc-99m-PYP imaging was examined in 12 cardiac transplant recipients. Two patients were studied on two occasions. The presence or absence of active rejection was established by endomyocardial biopsy. The intensity and pattern of myocardial uptake of the tracer did not differ significantly in the two patients studied at the time of rejection compared to the remainder. It is concluded that a single Tc-99m-PYP study cannot be used to diagnose cardiac transplant rejection.

    View details for Web of Science ID A1981MB41700010

    View details for PubMedID 6266731

  • EFFECTS OF BEDREST DECONDITIONING ON EXERCISE VENTRICULAR-FUNCTION IN MIDDLE-AGED MEN Hung, J., Goldwater, D., Convertino, V., McKillop, J., Goris, M., DeBusk, R. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 1981: 477–77
  • THE EFFECTS OF EXERCISE TRAINING ON MYOCARDIAL ISCHEMIA AND LEFT-VENTRICULAR FUNCTION SOON AFTER MYOCARDIAL-INFARCTION - A RANDOMIZED STUDY Hung, J., McKillop, J., Goris, M., DeBusk, R. LIPPINCOTT WILLIAMS & WILKINS. 1981: 198–98
  • Scintigraphic evaluation of coronary artery disease. Comprehensive therapy Goris, M. L., DeBusk, R. F. 1980; 6 (6): 18-26

    View details for PubMedID 7379489

  • INTRAOPERATIVE SKELETAL SCINTIGRAPHY FOR LOCALIZATION OF OSTEOID-OSTEOMA IN THE SPINE - CASE-REPORT JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME Rinsky, L. A., Goris, M., BLECK, E. E., Halpern, A., HIRSHMAN, P. 1980; 62 (1): 143-144

    View details for Web of Science ID A1980JC56500025

    View details for PubMedID 7351408

  • STATIC AND DYNAMIC STUDIES OF DEEP VENOUS THROMBOSIS AND ATHEROSCLEROSIS IN HUMANS WITH INDIUM-111-LABELED PLATELETS LANTIERI, R. L., Goodwin, D. A., GUTHANER, D., Conley, F., Goris, M. L., DOHERTY, P. W. BRITISH INST RADIOLOGY. 1980: 922–22
  • IN-111 PLATELET SCANNING IN CAROTID-ARTERY ATHEROSCLEROSIS LANTIERI, R. L., GUTHANER, D., Baumert, J., Conley, F., Goris, M. L., Goodwin, D. A. SOC NUCLEAR MEDICINE INC. 1980: P23–P23
  • THALLIUM IMAGING AND EXERCISE RADIONUCLIDE ANGIOGRAPHY FOR THE DETECTION OF RESIDUAL JEOPARDIZED MYOCARDIUM AFTER RECENT INFARCTION Hung, J., McKillop, J. H., Goris, M. L., SAVIN, W. M., DeBusk, R. F. SLACK INC. 1980: A182–A182
  • PHOTOPENIC LESIONS IN BONE-SCINTIGRAPHY CLINICAL NUCLEAR MEDICINE Goris, M. L., Basso, L. V., Etcubanas, E. 1980; 5 (7): 299-301

    Abstract

    Three cases with photopenic lesions on bone scintigraphy due to metastases from osteogenic sarcoma are presented.

    View details for Web of Science ID A1980KA84200003

    View details for PubMedID 6930338

  • Reliability and reproducibility of interpretation of 99mtechnetium pyrophosphate myocardial scintigrams. Clinical cardiology Mason, J. W., Myers, R. W., Goris, M. L., Doherty, P., Alderman, E. L., KRISS, J. P. 1979; 2 (6): 446-449

    Abstract

    The interpretations of 156 99mtechnetium pyrophosphate myocardial scintigrams by four observers were analyzed in order to determine the reliability and reproducibility of the subjective process of reading scintigrams. The scintigrams were scored on an integral scale from 0 to 4, depending upon the degree of myocardial radionuclide accumulation, and the site and nature of uptake were specified. Exact agreement upon score was generally poor but approximate concurrence of interpretation was good (90.4 and 92.5% inter- and intra-observer agreement, respectively). There was somewhat less agreement on scintigrams with the higher scores of 3 and 4 (83.3 and 78.0%, respectively). A high level of concurrence upon the differentiation between diffuse and localized uptake, and upon the site of uptake, was found. We conclude that only approximate rather than exact agreement of individual readers' interpretations can be expected in this subjective technique, that scintigrams with higher degrees of radionuclide accumulation produce slightly greater observer disagreement, and that variability of interpretation could account for some of the diagnostic inaccuracy of 99mtechnetium pyrophosphate myocardial scintigraphy.

    View details for PubMedID 232432

  • DETECTION OF OCCULT ABSCESSES WITH IN-111-LABELED LEUKOCYTES AMERICAN JOURNAL OF ROENTGENOLOGY Martin, W. R., Gurevich, N., Goris, M. L., McDougall, I. R. 1979; 133 (1): 123-125

    View details for Web of Science ID A1979GZ44100022

    View details for PubMedID 110043

  • CARDIAC DAMAGE PRODUCED BY DIRECT-CURRENT COUNTER-SHOCK APPLIED TO THE HEART AMERICAN JOURNAL OF CARDIOLOGY DOHERTY, P. W., McLaughlin, P. R., Billingham, M., Kernoff, R., Goris, M. L., HARRISON, D. C. 1979; 43 (2): 225-232

    Abstract

    This study examined the pathophysiology of the myocaridal damage produced by direct current shock over a dose range of 10 to 90 watt-seconds, applied directly to the heart in 26 dosgs. The extent of injury produced was assessed with creatine kinase depletion and light and electron microscopy, and was correlated with in vivo imaging and tissue distributions of the isotopes technetium-99m pyrophosphate and thallium-201. Changes in intramyocardial temperature and regional myocardial blood flow were also measured. Uptake of technetium-99m pyrophosphate occurred exponentially with graded increases in shocks, and this agent was more sensitive than thallium-201 in detecting injury both on imaging and at tissue level. The threshold for significant injury was approximately 30 watt-seconds, and on electron microscopy a characteristic feature was marked dehiscence of the intercalated disks between the damaged myocytes. The use of different-size paddles did not appear to affect the total number of cells damaged. However, with large paddles the injury was more superficial and spread over a wider area. With short time intervals between successive shocks, a greater amount of injury occurred, in part because of a compounding of the thermal component of the damage. Hypothermia can reduce the degree of injury.

    View details for Web of Science ID A1979GG62200008

    View details for PubMedID 760477

  • PYROPHOSPHATE RETENTION BY PREVIOUSLY IRRADIATED RENAL TISSUE RADIOLOGY LUTRIN, C. L., Goris, M. L. 1979; 133 (1): 207-209

    Abstract

    In 3 patients, each of whom had previously had part of one kidney included within the field during radiation therapy, whole-body bone imaging using 99mTc-pyrophosphate showed increased activity in the irradiated renal segment. Possible mechanisms of such renal uptake are discussed.

    View details for Web of Science ID A1979HN67500035

    View details for PubMedID 224416

  • RELATIVE EFFICACY OF RADIOGRAPHS AND BONE SCANS IN THE DETECTION OF THE SKELETAL LESIONS OF HISTIOCYTOSIS-X Parker, B. R., PINCKNEY, L. E., Etcubanas, E., Goris, M. L. AMER ROENTGEN RAY SOC. 1979: 307–8
  • PULMONARY ARTERIOVENOUS COMMUNICATIONS IN THE LUNG WESTERN JOURNAL OF MEDICINE Robin, E. D., Cummiskey, J., Robin, E. D., Theodore, J., Caughey, G., Goris, M., SALFEN, S. J., Hance, A., VANKESSEL, A., LYNNEDAVIES, P., Pinsky, M. 1979; 131 (1): 24-35

    View details for Web of Science ID A1979HF31300004

    View details for PubMedID 483788

  • INTENSE CONCENTRATION OF TECHNETIUM-99M PYROPHOSPHATE IN KIDNEYS OF CHILDREN TREATED WITH CHEMOTHERAPEUTIC DRUGS FOR MALIGNANT DISEASE RADIOLOGY LUTRIN, C. L., McDougall, I. R., Goris, M. L. 1978; 128 (1): 165-167

    Abstract

    Seventeen of 265 bone scans in children receiving chemotherapy for various malignant diseases exhibited intense renal parenchymal uptake of radioactivity during bone imaging. In a retrospective analysis, it was learned that uptake occurred when imaging was performed within one week of cancer chemotherapy. It was encountered after injection of cyclophosphamide (P less than 0.05), vincristine (P less than 0.01), and doxorubicin (P less than 0.02). In this series, none of the 265 scans showed intense renal uptake unless the patient received chemotherapeutic drugs in the preceding week. This finding did not seem to result from altered renal function, and the exact cause has not been defined.

    View details for Web of Science ID A1978FF24700028

    View details for PubMedID 663204

  • DECISION-MAKING AND IMAGE-PROCESSING IN NUCLEAR-MEDICINE IEEE TRANSACTIONS ON NUCLEAR SCIENCE Goris, M. L. 1978; 25 (2): 927-927
  • VALUE OF IN-111 CHLORIDE BONE-MARROW SCANNING IN DIFFERENTIAL-DIAGNOSIS OF BLOOD-COUNT DEPRESSION IN LYMPHOMA CANCER Gilbert, E. H., Glatstein, E., Goris, M. L., Earle, J. D. 1978; 41 (1): 143-152

    Abstract

    In patients with Hodgkin's disease or non-Hodgkin's lymphoma, the etiology of low peripheral blood counts is often difficult to determine. Often it is based on the results of a "random" bone marrow biopsy and/or aspirate, plus evaluation of circulating peripheral blood elements. However, these tests may be misleading. The present study evaluates the usefulness of 111Indium chloride bone marrow scanning in conjunction with marrow biopsies in distinguishing intrinsic from extrinsic causes for low peripheral blood counts. Thirty consecutive patients with Hodgkin's disease or non-Hodgkin's lymphoma, presenting with low peripheral blood counts and without any form of antineoplastic treatment for at least 5 weeks, were analyzed. Scan ratings were felt to be clinically accurate in 27 of the 30 patients analyzed (90%). In 18 patients (60%), the scan provided information which was not provided by any other standard test. 111Indium chloride scanning in conjunction with a marrow biopsy appears to be a useful, accurate means of evaluating bone marrow function in patients with depressed peripheral blood counts.

    View details for Web of Science ID A1978EK24400023

    View details for PubMedID 626925

  • BONE-MARROW REGENERATION FOLLOWING LARGE FIELD RADIATION - INFLUENCE OF VOLUME, AGE, DOSE, AND TIME CANCER SACKS, E. L., Goris, M. L., Glatstein, E., Gilbert, E., KAPLAN, H. S. 1978; 42 (3): 1057-1065

    Abstract

    Regeneration of bone marrow following radiation only was investigated using 111Indium as a bone scanning agent. Factors which influence local marrow regeneration are dose, age of the patient, and the total amount of the marrow which was irradiated. Time effects are not demonstrated in this study, except to the extent that most regeneration did occur within the first 12 months following irradiation. The most striking finding is the effect of the irradiation volume. Apparent inconsistencies in earlier reports concerning the dose effect could be explained by this effect alone.

    View details for Web of Science ID A1978FS88300003

    View details for PubMedID 100197

  • Krypton-81m. Progress in nuclear medicine Goris, M., DASPIT, S. 1978; 5: 69-92

    View details for PubMedID 748976

  • TC-99 BONE SCANNING IN EXPERIMENTAL OSTEOMYELITIS CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Rinsky, L., Goris, M. L., Schurman, D. J., Nagel, D. A. 1977: 361-366
  • REPRODUCIBILITY OF TL-201 MYOCARDIAL IMAGING/A CIRCULATION McLaughlin, P. R., Martin, R. P., Doherty, P., DASPIT, S., Goris, M., Haskell, W., Lewis, S., KRISS, J. P., HARRISON, D. C. 1977; 55 (3): 497-503

    Abstract

    Seventy-six thallium-201 myocardial perfusion studies were performed on twenty-five patients to assess their reproducibility and the effect ofvarying the level of exercise on the results of imaging. Each patient had a thallium-201 study at rest. Fourteen patients had studies on two occasions at maximum exercise, and twelve patients had studies both at light and at maximum exercise. Of 70 segments in the 14 patients assessed on each of two maximum exercise tests, 64 (91%) were reproducible. Only 53% (16/30) of the ischemic defects present at maximum exercise were seen in the light exercise study in the 12 patients assessed at two levels of exercise. Correlation of perfusion defects with arteriographically proven significant coronary stenosis was good for the left anterior descending and right coronary arteries, but not as good for circumflex artery disease. Thallium-201 myocardial imaging at maximum exercise is reproducible within acceptable limits, but careful attention to exercise technique is essential for valid comparative studies.

    View details for Web of Science ID A1977CX08700011

    View details for PubMedID 837485

  • TL-201 IMAGING FOR IDENTIFYING PATIENTS WITH CORONARY-ARTERY SPASM DOHERTY, P. W., Goris, M. L., ORLICK, A. E., Ricci, D. R., DASPIT, S. G., KRISS, J. P., HARRISON, D. C. LIPPINCOTT WILLIAMS & WILKINS. 1977: 230–30
  • TECHNETIUM-99M PYROPHOSPHATE MYOCARDIAL UPTAKE IN PATIENTS WITH STABLE ANGINA-PECTORIS AMERICAN JOURNAL OF CARDIOLOGY Mason, J. W., Myers, R. W., Alderman, E. L., Stinson, E. B., Goris, M. L., KRISS, J. P. 1977; 40 (1): 1-5

    Abstract

    99m-technetium (Tc) pyrophosphate myocardial scintigrams of 55 patients with stable angina pectoris were compared with those of 13 normal subjects. The mean scintigraphic score, obtained by averaging the blinded interpretations of four readers scoring on an integral scale from 0 to 4, was significantly higher for the patients with angina than for the control subjects (1.36 compared with 0.48, P less than 0.001). Among the patients with angina, those who had a prior myocardial infarction had a higher mean scintigraphic grade than those without a previous infarction (1.73 versus 1.15, P less than 0.005), and the mean grade in both groups was higher than that of control subjects (P less than 0.001). Radionuclide uptake was predominantly diffuse in the patients with angina pectoris (70%), although in those with greater uptake accumulation tended to be localized. Three of the 68 subjects had high levels of radionuclide uptake but no clinical evidence of acute myocardial injury. This study demonstrates that excess myocardial accumulation of 99m-Tc pyrophosphate can occur in patients with stable angina pectoris.

    View details for Web of Science ID A1977DM49800001

    View details for PubMedID 195451

  • MYOCARDIAL IMAGING IN A PATIENT WITH REPRODUCIBLE VARIANT ANGINA AMERICAN JOURNAL OF CARDIOLOGY McLaughlin, P. R., DOHERTY, P. W., Martin, R. P., Goris, M. L., HARRISON, D. C. 1977; 39 (1): 126-129

    Abstract

    A unique case is presented of variant angina pectoris with reproducible chest pain and S-T segment elevation in the immediate postexercise period and with normal coronary arteries. Coronary arterial spasm was deomnstrated with arteriography after intravenous administration of ergonivine maleate. Thallium-201 imaging during the pain reproducibility demonstrated malperfusion in the region supplied by the artery with documented spasm.

    View details for Web of Science ID A1977CS55900022

    View details for PubMedID 831419

  • APPLICATIONS OF VENTILATION LUNG IMAGING WITH KRYPTON-81M RADIOLOGY Goris, M. L., DASPIT, S. G., Walter, J. P., McRae, J., Lamb, J. 1977; 122 (2): 399-403

    Abstract

    A method for the evaluation of regional lung ventilation using 81mKr eluted from a rubidium generator is described. The tracer distribution at equilibrium is a function of regional ventilation, not of volumes. The study can be performed on a wide range of patients, including unconscious and mechanically ventilated patients, and can be performed immediately following or concurrently with a perfusion study. Thus, precisely comparable ventilation and perfusion images can be obtained.

    View details for Web of Science ID A1977CT87700028

    View details for PubMedID 834884

  • USE OF TL-201 IMAGING AFTER ERGONOVINE MALEATE INFUSION TO IDENTIFY CORONARY SPASM IN PATIENTS WITH ATYPICAL CHEST PAIN Doherty, P., Goris, M., Orlick, A., Ricci, D., DASPIT, S., KRISS, J., Harrison, D. SLACK INC. 1977: A217–A217
  • METHOD TO OPTIMIZE USE OF A GRAYSHADE SCALE IN NUCLEAR-MEDICINE IMAGES COMPUTERS AND BIOMEDICAL RESEARCH Goris, M. L., Scheibe, P. O., KRISS, J. P. 1976; 9 (6): 571-577

    View details for Web of Science ID A1976CR45400008

    View details for PubMedID 1000968

  • IN-111 BONE-MARROW SCINTIGRAPHY AS AN AID IN SELECTING MARROW BIOPSY SITES FOR EVALUATION OF MARROW ELEMENTS IN PATIENTS WITH LYMPHOMA CANCER Gilbert, E. H., Earle, J. D., Glatstein, E., Goris, M. L., KAPLAN, H. S., KRISS, J. P. 1976; 38 (4): 1560-1567

    Abstract

    One hundred and two previously treated lymphoma patients were studied with 111Indium bone marrow scans and bone marrow biopsies. The biopsies were considered to represent sampling errors when the cellularity of the biopsy did not reflect the general state of the marrow organ cellularity as demonstrated by the scan. In each instance the accuracy of the scan was confirmed by either another biopsy or the subsequent clinical course of the patient. Sampling errors were infrequent (1/51) in patients with normal peripheral blood counts and whose marrow had never been involved with tumor. Errors were especially likely (17/51) in patients who had had marrow involvement or those who had anemia, leukopenia, or thrombocytopenia. The 111Indium bone marrow scan allows the clinician to avoid selecting a biopsy site with a high risk for sampling error.

    View details for Web of Science ID A1976CJ83700018

    View details for PubMedID 991076

  • ACCURACY OF IN-111CL3 AS A BONE-MARROW SCANNING AGENT RADIOLOGY Gilbert, E. H., Earle, J. D., Goris, M. L., KAPLAN, H. S., KRISS, J. P. 1976; 119 (1): 167-168

    Abstract

    The number of normal cellular elements present in bone marrow biopsies was compared to the extent of uptake at corresponding sites on 111InCl3 bone marrow scans in 87 patients with malignant lymphoma. Of the biopsies free of tumor, 49/54 interpreted as normocellular and 16/17 hypocellular or aplastic confirmed the scan interpretation. Of the biopsies demonstrating tumor, 10/11 of those interpreted as normocellular and 14/15 hypocellular or aplastic confirmed the scan interpretation. The 111InCl3 bone marrow scan is accurate in depicting the presence or absence of normal marrow elements, but is of value in detecting tumor only when the normal elements are extensively replaced.

    View details for Web of Science ID A1976BK83900038

    View details for PubMedID 1257437

  • VESICLE INTERACTIONS WITH POLYAMINO ACIDS AND ANTIBODY - INVITRO AND INVIVO STUDIES JOURNAL OF NUCLEAR MEDICINE Dunnick, J. K., McDougall, I. R., Aragon, S., Goris, M. L., KRISS, J. P. 1975; 16 (6): 483-487

    Abstract

    Artificial spherules or vesicles of 900 A in diameter formed from phosphatidylcholine and gangliosides and enclosing 99mTcO4 - (standard preparation) survive intact in the circulation of the mouse. Polyamino acids and protein have been incorporated into and onto the vesicles; such vesicles remain intact as determined by diffusion dialysis studies and by electron paramagnetic resonance studies of vesicles enclosing spin label. In studying the distribution of polyamino acid-vesicles and protein vesicles in vivo, it was found that the latter distribute differently from standard vesicles or free protein alone whereas aromatic polyamino acid-vesicles concentrate in the liver and spleen to a greater extent than standard vesicles. We conclude that the permeability and stability characteristics of vesicles may be preserved when they are modified by the addition of protein or polyamino acids and that such modification of vesicles may be associated with an alteration of their fate in vivo. The potential exists to use vesicles as carriers of radiopharmaceuticals and other drugs and to direct the vesicles preferentially to tissue targets in vivo.

    View details for Web of Science ID A1975AD05200013

    View details for PubMedID 1159503

  • INVIVO DISTRIBUTION OF VESICLES LOADED WITH RADIOPHARMACEUTICALS - COMPARISON OF DIFFERENT ROUTES OF ADMINISTRATION SCOTTISH MEDICAL JOURNAL McDougall, I. R., Dunnick, J. K., Goris, M. L., KRISS, J. P. 1975; 20 (1): 39-39
  • INVIVO DISTRIBUTION OF VESICLES LOADED WITH RADIOPHARMACEUTICALS - STUDY OF DIFFERENT ROUTES OF ADMINISTRATION JOURNAL OF NUCLEAR MEDICINE McDougall, I. R., Dunnick, J. K., Goris, M. L., KRISS, J. P. 1975; 16 (6): 488-491

    Abstract

    The in vivo distribution of vesicles containing radiopharmaceuticals in their cavities has been studied using three routes of administration: intravenous, subcutaneous, and intraperitoneal. The in vivo distribution in mice was determined by dissection of the animals and calculation of radioactivity in the organs. In rats the in vivo distribution was assessed by scintigraphy using a scintillation camera-digital computer unit. After intravenous injection of vesicles, radioactivity is concentrated to some extent in the liver and spleen but the pattern of distribution is different from that of the corresponding free radiopharmaceutical or radiocolloid made of the corresponding radionuclide. The permeability of the vesicular membrane to contained radiopharmaceutical has been shown to vary according to the chemical composition of the vesicles. Vesicles can be used to introduce materials in vivo and the potential exists for their specific targeting by coupling other molecules to their surfaces.

    View details for Web of Science ID A1975AD05200014

    View details for PubMedID 1159504

  • In vivo distribution of vesicles loaded with radiopharmaceuticals: a comparison of different routes of administration. Scottish medical journal McDougall, I. R., Dunnick, J. K., Goris, M. L., Kris, J. P. 1975; 20 (1): 39-?

    View details for PubMedID 1111087