Shashi Singh

All Publications

• Applications of Artificial Intelligence for Pediatric Cancer Imaging. AJR. American journal of roentgenology Singh, S. B., Sarrami, A. H., Gatidis, S., Varniab, Z. S., Chaudhari, A., Daldrup-Link, H. E. 2024

  Abstract

  Artificial intelligence (AI) is transforming medical imaging of adult patients. However, its utilization in pediatric oncology imaging remains constrained, in part due to the inherent data scarcity associated with childhood cancers. Pediatric cancers are rare, and imaging technologies are evolving rapidly, leading to insufficient data of a particular type to effectively train these algorithms. The small market size of pediatrics compared to adults could also contribute to this challenge, as market size is a driver of commercialization. This article provides an overview of the current state of AI applications for pediatric cancer imaging, including applications for medical image acquisition, processing, reconstruction, segmentation, diagnosis, staging, and treatment response monitoring. While current developments are promising, impediments due to diverse anatomies of growing children and nonstandardized imaging protocols have led to limited clinical translation thus far. Opportunities include leveraging reconstruction algorithms to achieve accelerated low-dose imaging and automating the generation of metric-based staging and treatment monitoring scores. Transfer-learning of adult-based AI models to pediatric cancers, multi-institutional data sharing, and ethical data privacy practices for pediatric patients with rare cancers will be keys to unlocking AI's full potential for clinical translation and improved outcomes for these young patients.

  View details for DOI 10.2214/AJR.24.31076

  View details for PubMedID 38809123

• Detecting High-Dose Methotrexate-Induced Brain Changes in Pediatric and Young Adult Cancer Survivors Using [18F]FDG PET/MRI: A Pilot Study. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Baratto, L., Singh, S. B., Williams, S. E., Spunt, S. L., Rosenberg, J., Adams, L., Suryadevara, V., Iv, M., Daldrup-Link, H. 2024

  Abstract

  Significant improvements in treatments for children with cancer have resulted in a growing population of childhood cancer survivors who may face long-term adverse outcomes. Here, we aimed to diagnose high-dose methotrexate-induced brain injury on [18F]FDG PET/MRI and correlate the results with cognitive impairment identified by neurocognitive testing in pediatric cancer survivors. Methods: In this prospective, single-center pilot study, 10 children and young adults with sarcoma (n = 5), lymphoma (n = 4), or leukemia (n = 1) underwent dedicated brain [18F]FDG PET/MRI and a 2-h expert neuropsychologic evaluation on the same day, including the Wechsler Abbreviated Scale of Intelligence, second edition, for intellectual functioning; Delis-Kaplan Executive Function System (DKEFS) for executive functioning; and Wide Range Assessment of Memory and Learning, second edition (WRAML), for verbal and visual memory. Using PMOD software, we measured the SUVmean, cortical thickness, mean cerebral blood flow (CBFmean), and mean apparent diffusion coefficient of 3 different cortical regions (prefrontal cortex, cingulate gyrus, and hippocampus) that are routinely involved during the above-specified neurocognitive testing. Standardized scores of different measures were converted to z scores. Pairs of multivariable regression models (one for z scores < 0 and one for z scores > 0) were fitted for each brain region, imaging measure, and test score. Heteroscedasticity regression models were used to account for heterogeneity in variances between brain regions and to adjust for clustering within patients. Results: The regression analysis showed a significant correlation between the SUVmean of the prefrontal cortex and cingulum and DKEFS-sequential tracking (DKEFS-TM4) z scores (P = 0.003 and P = 0.012, respectively). The SUVmean of the hippocampus did not correlate with DKEFS-TM4 z scores (P = 0.111). The SUVmean for any evaluated brain regions did not correlate significantly with WRAML-visual memory (WRAML-VIS) z scores. CBFmean showed a positive correlation with SUVmean (r = 0.56, P = 0.01). The CBFmean of the cingulum, hippocampus, and prefrontal cortex correlated significantly with DKEFS-TM4 (all P < 0.001). In addition, the hippocampal CBFmean correlated significantly with negative WRAML-VIS z scores (P = 0.003). Conclusion: High-dose methotrexate-induced brain injury can manifest as a reduction in glucose metabolism and blood flow in specific brain areas, which can be detected with [18F]FDG PET/MRI. The SUVmean and CBFmean of the prefrontal cortex and cingulum can serve as quantitative measures for detecting executive functioning problems. Hippocampal CBFmean could also be useful for monitoring memory problems.

  View details for DOI 10.2967/jnumed.123.266760

  View details for PubMedID 38575193

• Machine learning in the positron emission tomography imaging of Alzheimer's disease. Nuclear medicine communications Ayubcha, C., Singh, S. B., Patel, K. H., Rahmim, A., Hasan, J., Liu, L., Werner, T., Alavi, A. 2023

  Abstract

  The utilization of machine learning techniques in medicine has exponentially increased over the last decades due to innovations in computer processing, algorithm development, and access to big data. Applications of machine learning techniques to neuroimaging specifically have unveiled various hidden interactions, structures, and mechanisms related to various neurological disorders. One application of interest is the imaging of Alzheimer's disease, the most common cause of progressive dementia. The diagnoses of Alzheimer's disease, mild cognitive impairment, and preclinical Alzheimer's disease have been difficult. Molecular imaging, particularly via PET scans, holds tremendous value in the imaging of Alzheimer's disease. To date, many novel algorithms have been developed with great success that leverage machine learning in the context of Alzheimer's disease. This review article provides an overview of the diverse applications of machine learning to PET imaging of Alzheimer's disease.

  View details for DOI 10.1097/MNM.0000000000001723

  View details for PubMedID 37395538

• Multimodal Pediatric Lymphoma Detection using PET and MRI. AMIA ... Annual Symposium proceedings. AMIA Symposium Wang, H., Sarrami, A., Wu, J. T., Baratto, L., Sharma, A., Wong, K. C., Singh, S. B., Daldrup-Link, H. E., Syeda-Mahmood, T. 2023; 2023: 736-743

  Abstract

  Lymphoma is one of the most common types of cancer for children (ages 0 to 19). Due to the reduced radiation exposure, PET/MR systems that allow simultaneous PET and MR imaging have become the standard of care for diagnosing cancers and monitoring tumor response to therapy in the pediatric population. In this work, we developed a multimodal deep learning algorithm for automatic pediatric lymphoma detection using PET and MRI. Through innovative designs such as standardized uptake value (SUV) guided tumor candidate generation, location aware classification model learning and weighted multimodal feature fusion, our algorithm can be effectively trained with limited data and achieved superior tumor detection performance over the state-of-the-art in our experiments.

  View details for PubMedID 38222333

  View details for PubMedCentralID PMC10785920

• The effects of limb laterality and age on the inflammation and bone turnover of the acromioclavicular shoulder joint: 18 F-fluorodeoxyglucose and 18 F-sodium-fluoride-PET/computed tomography study. Nuclear medicine communications Park, P. S., McDonald, E., Singh, S. B., Raynor, W. Y., Werner, T. J., Høilund-Carlsen, P. F., Alavi, A. 2022; 43 (8): 922-927

  Abstract

  The acromioclavicular (AC) joint is a common site of injury and degenerative changes such as osteoarthritis (OA) of the shoulder. Physical manifestations of OA are preceded by molecular changes, detection of which may enhance early prophylaxis and monitoring of disease progression. In this study, we investigate the use of 18 F-FDG and 18 F-NaF-PET/CT to assess the effects of limb laterality and age on the inflammation and bone turnover of the AC shoulder joint.We analyzed FDG and NaF-PET/CT scans of 41 females (mean age of 43.9 ± 14.2 years) and 45 males (mean age of 44.5 ± 13.8 years) using a semiquantitative technique based on predefined ROI.There was a greater NaF uptake in the right side of the AC joint compared with the left in both females (left: 2.22 ± 1.00; right: 3.08 ± 1.18; P < 0.0001) and males (left: 2.57 ± 1.49; right: 2.99 ± 1.40; P = 0.003). No consistent correlation between age and NaF or FDG uptakes were found in both females and males. There was also a positive correlation between FDG and NaF uptakes in both left ( P = 0.01; r = 0.37) and right ( P = 0.0006; r = 0.53) AC joints of male subjects.Our study is the first to reveal the varying effect of right-left limb laterality and aging on FDG and NaF uptake at the AC joint. Future studies correlating the history of shoulder trauma, pain, and degenerative change with FDG and NaF-PET/CT findings will be critical in the adoption of molecular imaging in the clinical setting.

  View details for DOI 10.1097/MNM.0000000000001588

  View details for PubMedID 35634806

• [18F]FDG PET/CT for identifying the causes of fever of unknown origin (FUO). American journal of nuclear medicine and molecular imaging Singh, S. B., Shrestha, N., Bhandari, S., Shrestha, S., Shrestha, B., Shrestha, N., Rijal, S., Singh, R., Hess, S., Werner, T. J., Alavi, A., Revheim, M. E. 2024; 14 (2): 87-96

  Abstract

  Fever of unknown origin (FUO) continues to be a challenging diagnosis in clinical medicine. It has more than 200 known causes, including infections, autoimmune diseases, neoplasia, and other miscellaneous disorders. Despite the development of a wide range of diagnostic tools, a specific diagnostic algorithm for FUO is not yet available. However, [18F]FDG PET/CT, which yields information on cellular metabolism, in addition to details of organ anatomy, has been shown to be successful in the FUO investigation. This study highlights the uses of [18F]FDG PET/CT in diagnosing various causes of FUO. [18F]FDG PET/CT has been increasingly used to detect septic infections, sterile inflammatory processes, and malignancies, occupying a significant portion of the known causes of FUO. It has led to a more definitive identification of the etiology of FUO and accurate clinical management. However, more in-depth studies are crucial to understanding if [18F]FDG PET/CT can be used in the work-up of FUO.

  View details for DOI 10.62347/OQQC6007

  View details for PubMedID 38737639

  View details for PubMedCentralID PMC11087293

• The utility of PET imaging in depression. Frontiers in psychiatry Singh, S. B., Tiwari, A., Katta, M. R., Kafle, R., Ayubcha, C., Patel, K. H., Bhattarai, Y., Werner, T. J., Alavi, A., Revheim, M. E. 2024; 15: 1322118

  Abstract

  This educational review article aims to discuss growing evidence from PET studies in the diagnosis and treatment of depression. PET has been used in depression to explore the neurotransmitters involved, the alterations in neuroreceptors, non-neuroreceptor targets (e.g., microglia and astrocytes), the severity and duration of the disease, the pharmacodynamics of various antidepressants, and neurobiological mechanisms of non-pharmacological therapies like psychotherapy, electroconvulsive therapy, and deep brain stimulation therapy, by showing changes in brain metabolism and receptor and non-receptor targets. Studies have revealed alterations in neurotransmitter systems such as serotonin, dopamine, GABA, and glutamate, which are linked to the pathophysiology of depression. Overall, PET imaging has furthered the neurobiological understanding of depression. Despite these advancements, PET findings have not yet led to significant changes in evidence-based practices. Addressing the reasons behind inconsistencies in PET imaging results, conducting large sample size studies with a more standardized methodological approach, and investigating further the genetic and neurobiological aspects of depression may better leverage PET imaging in future studies.

  View details for DOI 10.3389/fpsyt.2024.1322118

  View details for PubMedID 38711875

  View details for PubMedCentralID PMC11070570

• Molecular Imaging Techniques in the Diagnosis and Monitoring of Infectious Diseases CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES Thorsen, M., Singh, S. B., Rewers, K., Werner, T. J., Alavi, A., Hess, S. 2024

  View details for DOI 10.1007/s40506-024-00274-1

  View details for Web of Science ID 001195684500001

• Role of PET/CT in diagnosing and monitoring disease activity in rheumatoid arthritis: a review. Annals of nuclear medicine Singh, S. B., Bhandari, S., Bhandari, S., Bhandari, S., Singh, R., Raynor, W. Y., Hess, S., Werner, T. J., Alavi, A., Revheim, M. 2024

  Abstract

  Rheumatoid Arthritis (RA) is a systemic inflammatory disorder that commonly presents with polyarthritis but can have multisystemic involvement and complications, leading to increased morbidity and mortality. The diagnosis of RA continues to be challenging due to its varied clinical presentations. In this review article, we aim to determine the potential of PET/CT to assist in the diagnosis of RA and its complications, evaluate the therapeutic response to treatment, and predict RA remission. PET/CT has increasingly been used in the last decade to diagnose, monitor treatment response, predict remissions, and diagnose subclinical complications in RA. PET imaging with [18F]-fluorodeoxyglucose ([18F]-FDG) is the most commonly applied radiotracer in RA, but other tracers are also being studied. PET/CT with [18F]-FDG, [18F]-NaF, and other tracers might lead to early identification of RA and timely evidence-based clinical management, decreasing morbidity and mortality. Although PET/CT has been evolving as a promising tool for evaluating and managing RA, more evidence is required before incorporating PET/CT in the standard clinical management of RA.

  View details for DOI 10.1007/s12149-023-01896-z

  View details for PubMedID 38277115

• PET/CT in the Evaluation of CAR-T Cell Immunotherapy in Hematological Malignancies Molecular Imaging Singh, S. B., Bhandari, S., Siwakoti, S., Singh, R., Bhusal, S., Sharma, K., Bhandari, S., Khanal, K. 2024; 23: 15353508241257924

  View details for DOI 10.1177/15353508241257924

• Neurological and Psychiatric Manifestations of Long COVID-19 and Their [18F]FDG PET Findings: A Review. Diagnostics (Basel, Switzerland) Hameed, R., Bahadur, A. R., Singh, S. B., Sher, J., Todua, M., Moradi, L. M., Bastakoti, S., Arslan, M., Ajmal, H., Lee, G. Y., Ayubcha, C., Werner, T. J., Alavi, A., Revheim, M. E. 2023; 13 (14)

  Abstract

  For more than two years, lingering sequalae of COVID-19 have been extensively investigated. Approximately 10% of individuals infected by COVID-19 have been found to experience long-term symptoms termed "long COVID-19". The neurological and psychiatric manifestations of long COVID-19 are of particular concern. While pathogenesis remains unclear, emerging imaging studies have begun to better elucidate certain pathological manifestation. Of specific interest is imaging with [18F]FDG PET which directly reflects cellular glycolysis often linked to metabolic and inflammatory processes. Seeking to understand the molecular basis of neurological features of long COVID-19, this review encompasses the most recent [18F]FDG PET literature in this area.

  View details for DOI 10.3390/diagnostics13142353

  View details for PubMedID 37510097

• Is Imaging Bacteria with PET a Realistic Option or an Illusion? Diagnostics (Basel, Switzerland) Singh, S. B., Bhandari, S., Siwakoti, S., Bhatta, R., Raynor, W. Y., Werner, T. J., Alavi, A., Hess, S., Revheim, M. E. 2023; 13 (7)

  Abstract

  The application of [18F]-fluorodeoxyglucose ([18F]FDG) as a radiotracer to detect sites of inflammation (either due to bacterial infection or primary inflammation) has led to exploring the role of PET in visualizing bacteria directly at sites of infection. However, the results from such efforts are controversial and inconclusive so far. We aimed to assess the limitations of PET as an effective modality in the diagnosis of bacterial infections. Inflammation due to bacterial infections can be visualized by using [18F]FDG-PET. However, the non-specificity of [18F]FDG makes it undesirable to visualize bacteria as the underlying cause of inflammation. Hence, more specific radiotracers that possibly bind to or accumulate in bacteria-specific receptors or enzymes are being explored. Several radiotracers, including 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS), 6-[18F]-fluoromaltose, [11C]para-aminobenzoic acid ([11C]PABA), radiolabeled trimethoprim (11C-TMP) and its analog fluoropropyl-trimethoprim (18F-FPTMP), other radiolabeled sugars, and antimicrobial drugs have been used to image microorganisms. Unfortunately, no progress has been made in translating the results to routine human use; feasibility and other factors have constrained their success in clinical settings. In the current article, we discuss the limitations of direct bacterial visualization with PET tracers, but emphasize the important role of [18F]FDG-PET as the only option for detecting evidence of infection.

  View details for DOI 10.3390/diagnostics13071231

  View details for PubMedID 37046449

  View details for PubMedCentralID PMC10093025

• Emerging PET Tracers in Cardiac Molecular Imaging. Cardiology and therapy Singh, S. B., Ng, S. J., Lau, H. C., Khanal, K., Bhattarai, S., Paudyal, P., Shrestha, B. B., Naseer, R., Sandhu, S., Gokhale, S., Raynor, W. Y. 2023; 12 (1): 85-99

  Abstract

  18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) represent emerging PET tracers used to assess atherosclerosis-related inflammation and molecular calcification, respectively. By localizing to sites with high glucose utilization, FDG has been used to assess myocardial viability for decades, and its role in evaluating cardiac sarcoidosis has come to represent a major application. In addition to determining late-stage changes such as loss of perfusion or viability, by targeting mechanisms present in atherosclerosis, PET-based techniques have the ability to characterize atherogenesis in the early stages to guide intervention. Although it was once thought that FDG would be a reliable indicator of ongoing plaque formation, micro-calcification as portrayed by NaF-PET/CT appears to be a superior method of monitoring disease progression. PET imaging with NaF has the additional advantage of being able to determine abnormal uptake due to coronary artery disease, which is obscured by physiologic myocardial activity on FDG-PET/CT. In this review, we discuss the evolving roles of FDG, NaF, and other PET tracers in cardiac molecular imaging.

  View details for DOI 10.1007/s40119-022-00295-1

  View details for PubMedID 36593382

  View details for PubMedCentralID PMC9986170

• Dual time-point imaging of lymphoma adenopathy using total-body FDG PET/CT Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting 2023 Shrestha, B., Singh, S., Motamedi, N., Werner, T., Nardo, L., Abdelhafez, Y., Alavi, A. 2023: P1444-P1444
• Chimeric antigen receptor T-cell treatment for non-Hodgkin lymphoma: A comprehensive bone marrow evaluation with FDG PET/CT Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting 2023 Shrestha, B., Singh, S., Ismoilov, M., Niazi, S., Ahmed, M., Motamedi, N., Werner, T., Revheim, M., Høilund-Carlsen, P., Alavi, A., Raynor, W. 2023: P1342-P1342
• Effects of chimeric antigen receptor T-cell therapy on pulmonary and hepatic FDG uptake in patients with non-Hodgkin lymphoma Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting 2023 Shrestha, B., Singh, S., Raynor, W., Ahmed, M., Valluru, S., Singh, R., Glennan, P., Shehu, V., Werner, T., Revheim, M., Høilund-Carlsen, P., Alavi, A. 2023: P1076-P1076
• The evolving role of [18F] DCFPyL (Pylarify) PET/CT in the management of Prostate Cancer Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting 2023 Jasaraj, R., Khanal, K., Bhusal, S., Shrestha, B., Singh, S. 2023: P1443-P1443
• Role of 18F-FDG PET/CT to evaluate the effects of chimeric antigen receptor T-cell therapy on lymph node involvement in patients with non-Hodgkin lymphoma Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting 2023 Shrestha, B., Singh, S., Raynor, W., Niazi, S., Ahmed, M., Ismoilov, M., Motamedi, N., Werner, T., Revheim, M., Høilund-Carlsen, P., Alavi, A. 2023: P1159-P1159
• A Review of 177Lutetium-PSMA and 225Actinium-PSMA as Emerging Theranostic Agents in Prostate Cancer. Cureus Alam, M. R., Singh, S. B., Thapaliya, S., Shrestha, S., Deo, S., Khanal, K. 2022; 14 (9): e29369

  Abstract

  The development of prostate-specific membrane antigen (PSMA) ligands labeled with radionuclides is a ground-breaking achievement in the management of prostate cancer. With the increasing use of 68Gallium-PSMA and 18F-DCFPyL (Pylarify) and their approval by the Food and Drug Administration (FDA), other PSMA agents and their unique characteristics are also being studied. Two other PSMA agents, namely 177Lutetium-PSMA (177Lu-PSMA) and 225Actinium-PSMA (225Ac-PSMA), are currently drawing the researcher's attention mainly due to their theranostic importance. Studies focusing on the essential characteristics of these two emerging radiotracers are relatively lacking. Hence, this review article, beginning with a brief introduction, intends to provide insights on the mechanism, efficacy, adverse effects, usefulness, including theranostic implications, and limitations of these two emerging PSMA agents. The 177Lu-PSMA is commercially accessible, is well tolerated, and has been found to lower prostate-specific antigen (PSA) levels while improving patients' quality of life. It also reduces pain and the requirement for analgesics and is safe for advanced diseases. However, despite its potential advantages, around one-third of patients do not respond satisfactorily to this costly treatment; it is still challenging to personalize this therapy and predict its outcome. Similarly, 225Ac is compatible with antibody-based targeting vectors, releasing four extremely hazardous high-energy emissions with a longer half-life of 10 days. It has made 225Ac-PSMA therapy useful for tumors resistant to standard treatments, with a better response than 177Lu-PSMA. Dosimetry studies show a good biochemical response without toxicity in patients with advanced metastatic castration-resistant prostate cancer (mCRPC). However, it can potentially cause significant damage to healthy tissues if not retained at the tumor site. Encapsulating radionuclides in a nano-carrier, hastening the absorption by tumor cells, and local delivery might all help reduce the harmful consequences. Both have advantages and disadvantages. The choice of PSMA agents may rely on desired qualities, cost, and convenience, among other factors. Further research is warranted in order to better understand their ideal use in clinical settings.

  View details for DOI 10.7759/cureus.29369

  View details for PubMedID 36284803

  View details for PubMedCentralID PMC9584169

• Examining the role of FDG-PET/CT in early diagnosis and assessment of venous thromboembolism (VTE) Singh, S., Griffin, M., Revheim, M., Saboury, B., Werner, T., Alavi, A., Hess, S. SOC NUCLEAR MEDICINE INC. 2022

  View details for Web of Science ID 000893739700045

• Comparison of Global cardiac atherosclerosis burden with Alavi-Carlsen Calcification score (ACCS) relative to coronary artery calcification score (CACS) Khanal, K., Singh, S., Revheim, M., Saboury, B., Werner, T., Alavi, A. SOC NUCLEAR MEDICINE INC. 2022

  View details for Web of Science ID 000893739700046

• Is Imaging of Bacteria with PET a realistic goal? Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2022 Annual Meeting Singh, S., Raynor, W., Revheim, M., Saboury, B., Werner, T., Alavi, A., Hess, S. 2022: 2677-2677
• The evolving role of FAPI-PET in assessing patients with various malignancies and its potential superiority over FDG-PET in this setting Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2022 Annual Meeting Singh, S., Khurana, N. K., Saboury, B., Werner, T., Alavi, A., Revheim, M. 2022: 2711-2711
• Role of Natalizumab in Relapsing-Remitting Multiple Sclerosis: A review. Journal of Brain and Spine Foundation Nepal Paudel, A. K., Bastakoti, S., Dulal, N. R., Piya, G., Singh, S. B. 2021; 2 (1): 2-12
• Empowering Nepalese Villagers with Health Literacy through Maintenance of Personal Health Records in a Health Database Sonoda journal Sugino, M., Naito, T., Kanbara, M., Sawabe, T., Mizohata, S., Sawabe, M., Lama, N., Tamang, M., Jha, R., Shrestha, B., Dahal, M., Acharya, B., Shah, A., Thapa, B., Shrestha, S., Bhattarai, P., Singh, S., Khadka, A., Pandey, S., Maharjan, S., Mandal, S. 2020; 1: 45-54
• Addiction Psychiatry Training Experience, Belief about Addiction and Brief Screening for Substance Use among Medical Interns: A Cross-Sectional Survey Journal of Psychiatrists Association of Nepal Pokhrel, P. 2019; 8 (1): 45–49

  View details for DOI 10.3126/jpan.v8i1.26336