Richard E. Fan, Ph.D., is an engineer embedded in the Department of Urology in the Stanford School of Medicine.
Dr. Fan’s research relates to the development of clinically driven biomedical instrumentation and medical devices. He is interested in translational application of emerging technologies in the medical and surgical spaces, as well as the development of platforms to explore clinical and pre-clinical evaluation. His primary work is currently focused on image guided detection and treatment of prostate cancer, including MR-US fusion, focal therapies, embedded systems and robotics.
Clinical Assistant Professor, Urology
Engineering Director, Urologic Cancer Innovation Lab (2014 - Present)
Undergraduate Programs, Stanford Byers Center for Biodesign (2017 - Present)
PhD, UCLA, Biomedical Engineering (2010)
MS, UCLA, Electrical Engineering (2006)
BS, University of Arizona, Electrical Engineering (2005)
- Biodesign Fundamentals
MED 175B (Spr)
- Biodesign Fundamentals
MED 275B (Spr)
- Biodesign: Need in Finding Healthcare
MED 260 (Aut)
- Senior Capstone Design I
BIOE 141A (Aut)
- Senior Capstone Design II
BIOE 141B (Win)
- Independent Studies (3)
Prior Year Courses
- Biodesign Fundamentals
MED 175B (Spr)
- Biodesign Fundamentals
MED 275B (Spr)
- Biodesign: Seminar in Need-Driven Medical Innovation
MED 260 (Spr)
- Senior Capstone Design I
BIOE 141A (Aut)
- Senior Capstone Design II
BIOE 141B (Win)
- Biodesign Fundamentals
MED 275B (Spr)
- Senior Capstone Design I
BIOE 141A (Aut)
- Senior Capstone Design II
BIOE 141B (Win)
- Biodesign Fundamentals
Multi-institutional analysis of clinical and imaging risk factors for detecting clinically significant prostate cancer in men with PI-RADS 3 lesions.
BACKGROUND: Most Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions do not contain clinically significant prostate cancer (CSPCa; grade group ≥2). This study was aimed at identifying clinical and magnetic resonance imaging (MRI)-derived risk fac- tors that predict CSPCa in men with PI-RADS 3 lesions.METHODS: This study analyzed the detection of CSPCa in men who underwent MRI-targeted biopsy for PI-RADS 3 lesions. Multivariable logistic regression models with goodness-of-fit testing were used to identify variables associated with CSPCa. Receiver operating curves and decision curve analyses were used to estimate the clinical utility of a predictive model.RESULTS: Of the 1784 men reviewed, 1537 were included in the training cohort, and 247 were included in the validation cohort. The 309 men with CSPCa (17.3%) were older, had a higher prostate-specific antigen (PSA) density, and had a greater likelihood of an anteriorly located lesion than men without CSPCa (p < .01). Multivariable analysis revealed that PSA density (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.05-1.85; p < .01), age (OR, 1.05; 95% CI, 1.02-1.07; p < .01), and a biopsy-naive status (OR, 1.83; 95% CI, 1.38-2.44) were independently associated with CSPCa. A prior negative biopsy was negatively associated (OR, 0.35; 95% CI, 0.24-0.50; p < .01). The application of the model to the validation cohort resulted in an area under the curve of 0.78. A predicted risk threshold of 12% could have prevented 25% of biopsies while detecting almost 95% of CSPCas with a sensitivity of 94% and a specificity of 34%.CONCLUSIONS: For PI-RADS 3 lesions, an elevated PSA density, older age, and a biopsy-naive status were associated with CSPCa, whereas a prior negative biopsy was negatively associated. A predictive model could prevent PI-RADS 3 biopsies while missing few CSPCas.LAY SUMMARY: Among men with an equivocal lesion (Prostate Imaging-Reporting and Data System 3) on multiparametric magnetic resonance imaging (mpMRI), those who are older, those who have a higher prostate-specific antigen density, and those who have never had a biopsy before are at higher risk for having clinically significant prostate cancer (CSPCa) on subsequent biopsy. However, men with at least one negative biopsy have a lower risk of CSPCa. A new predictive model can greatly reduce the need to biopsy equivocal lesions noted on mpMRI while missing only a few cases of CSPCa.
View details for DOI 10.1002/cncr.34355
View details for PubMedID 35819253
Computational Detection of Extraprostatic Extension of Prostate Cancer on Multiparametric MRI Using Deep Learning.
2022; 14 (12)
The localization of extraprostatic extension (EPE), i.e., local spread of prostate cancer beyond the prostate capsular boundary, is important for risk stratification and surgical planning. However, the sensitivity of EPE detection by radiologists on MRI is low (57% on average). In this paper, we propose a method for computational detection of EPE on multiparametric MRI using deep learning. Ground truth labels of cancers and EPE were obtained in 123 patients (38 with EPE) by registering pre-surgical MRI with whole-mount digital histopathology images from radical prostatectomy. Our approach has two stages. First, we trained deep learning models using the MRI as input to generate cancer probability maps both inside and outside the prostate. Second, we built an image post-processing pipeline that generates predictions for EPE location based on the cancer probability maps and clinical knowledge. We used five-fold cross-validation to train our approach using data from 74 patients and tested it using data from an independent set of 49 patients. We compared two deep learning models for cancer detection: (i) UNet and (ii) the Correlated Signature Network for Indolent and Aggressive prostate cancer detection (CorrSigNIA). The best end-to-end model for EPE detection, which we call EPENet, was based on the CorrSigNIA cancer detection model. EPENet was successful at detecting cancers with extraprostatic extension, achieving a mean area under the receiver operator characteristic curve of 0.72 at the patient-level. On the test set, EPENet had 80.0% sensitivity and 28.2% specificity at the patient-level compared to 50.0% sensitivity and 76.9% specificity for the radiologists. To account for spatial location of predictions during evaluation, we also computed results at the sextant-level, where the prostate was divided into sextants according to standard systematic 12-core biopsy procedure. At the sextant-level, EPENet achieved mean sensitivity 61.1% and mean specificity 58.3%. Our approach has the potential to provide the location of extraprostatic extension using MRI alone, thus serving as an independent diagnostic aid to radiologists and facilitating treatment planning.
View details for DOI 10.3390/cancers14122821
View details for PubMedID 35740487
Bridging the gap between prostate radiology and pathology through machine learning.
Prostate cancer remains the second deadliest cancer for American men despite clinical advancements. Currently, Magnetic Resonance Imaging (MRI) is considered the most sensitive non-invasive imaging modality that enables visualization, detection and localization of prostate cancer, and is increasingly used to guide targeted biopsies for prostate cancer diagnosis. However, its utility remains limited due to high rates of false positives and false negatives as well as low inter-reader agreements.Machine learning methods to detect and localize cancer on prostate MRI can help standardize radiologist interpretations. However, existing machine learning methods vary not only in model architecture, but also in the ground truth labeling strategies used for model training. We compare different labeling strategies and the effects they have on the performance of different machine learning models for prostate cancer detection on MRI.Four different deep learning models (SPCNet, U-Net, branched U-Net, and DeepLabv3+) were trained to detect prostate cancer on MRI using 75 patients with radical prostatectomy, and evaluated using 40 patients with radical prostatectomy and 275 patients with targeted biopsy. Each deep learning model was trained with four different label types: pathology-confirmed radiologist labels, pathologist labels on whole-mount histopathology images, and lesion-level and pixel-level digital pathologist labels (previously validated deep learning algorithm on histopathology images to predict pixel-level Gleason patterns) on whole-mount histopathology images. The pathologist and digital pathologist labels (collectively referred to as pathology labels) were mapped onto pre-operative MRI using an automated MRI-histopathology registration platform.Radiologist labels missed cancers (ROC-AUC: 0.75 - 0.84), had lower lesion volumes (~68% of pathology lesions), and lower Dice overlaps (0.24 - 0.28) when compared with pathology labels. Consequently, machine learning models trained with radiologist labels also showed inferior performance compared to models trained with pathology labels. Digital pathologist labels showed high concordance with pathologist labels of cancer (lesion ROC-AUC: 0.97 - 1, lesion Dice: 0.75 - 0.93). Machine learning models trained with digital pathologist labels had the highest lesion detection rates in the radical prostatectomy cohort (aggressive lesion ROC-AUC: 0.91 - 0.94), and had generalizable and comparable performance to pathologist label trained-models in the targeted biopsy cohort (aggressive lesion ROC-AUC: 0.87 - 0.88), irrespective of the deep learning architecture. Moreover, machine learning models trained with pixel-level digital pathologist labels were able to selectively identify aggressive and indolent cancer components in mixed lesions on MRI, which is not possible with any human-annotated label type.Machine learning models for prostate MRI interpretation that are trained with digital pathologist labels showed higher or comparable performance with pathologist label-trained models in both radical prostatectomy and targeted biopsy cohort. Digital pathologist labels can reduce challenges associated with human annotations, including labor, time, inter- and intra-reader variability, and can help bridge the gap between prostate radiology and pathology by enabling the training of reliable machine learning models to detect and localize prostate cancer on MRI. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/mp.15777
View details for PubMedID 35633505
Correlation of 68Ga-RM2 PET with Post-Surgery Histopathology Findings in Patients with Newly Diagnosed Intermediate- or High-Risk Prostate Cancer.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Rationale: 68Ga-RM2 targets gastrin-releasing peptide receptors (GRPR), which are overexpressed in prostate cancer (PC). Here, we compared pre-operative 68Ga-RM2 PET to post-surgery histopathology in patients with newly diagnosed intermediate- or high-risk PC. Methods: Forty-one men, 64.0+/-6.7-year-old, were prospectively enrolled. PET images were acquired 42 - 72 (median+/-SD 52.5+/-6.5) minutes after injection of 118.4 - 247.9 (median+/-SD 138.0+/-22.2)MBq of 68Ga-RM2. PET findings were compared to pre-operative mpMRI (n = 36) and 68Ga-PSMA11 PET (n = 17) and correlated to post-prostatectomy whole-mount histopathology (n = 32) and time to biochemical recurrence. Nine participants decided to undergo radiation therapy after study enrollment. Results: All participants had intermediate (n = 17) or high-risk (n = 24) PC and were scheduled for prostatectomy. Prostate specific antigen (PSA) was 8.8+/-77.4 (range 2.5 - 504) ng/mL, and 7.6+/-5.3 (range 2.5 - 28.0) ng/mL when excluding participants who ultimately underwent radiation treatment. Pre-operative 68Ga-RM2 PET identified 70 intraprostatic foci of uptake in 40/41 patients. Post-prostatectomy histopathology was available in 32 patients in which 68Ga-RM2 PET identified 50/54 intraprostatic lesions (detection rate = 93%). 68Ga-RM2 uptake was recorded in 19 non-enlarged pelvic lymph nodes in 6 patients. Pathology confirmed lymph node metastases in 16 lesions, and follow-up imaging confirmed nodal metastases in 2 lesions. 68Ga-PSMA11 and 68Ga-RM2 PET identified 27 and 26 intraprostatic lesions, respectively, and 5 pelvic lymph nodes each in 17 patients. Concordance between 68Ga-RM2 and 68Ga-PSMA11 PET was found in 18 prostatic lesions in 11 patients, and 4 lymph nodes in 2 patients. Non-congruent findings were observed in 6 patients (intraprostatic lesions in 4 patients and nodal lesions in 2 patients). Both 68Ga-RM2 and 68Ga-PSMA11 had higher sensitivity and accuracy rates with 98%, 89%, and 95%, 89%, respectively, compared to mpMRI at 77% and 77%. Specificity was highest for mpMRI with 75% followed by 68Ga-PSMA11 (67%), and 68Ga-RM2 (65%). Conclusion: 68Ga-RM2 PET accurately detects intermediate- and high-risk primary PC with a detection rate of 93%. In addition, it showed significantly higher specificity and accuracy compared to mpMRI and similar performance to 68Ga-PSMA11 PET. These findings need to be confirmed in larger studies to identify which patients will benefit from one or the other or both radiopharmaceuticals.
View details for DOI 10.2967/jnumed.122.263971
View details for PubMedID 35552245
Image quality assessment for machine learning tasks using meta-reinforcement learning.
Medical image analysis
2022; 78: 102427
In this paper, we consider image quality assessment (IQA) as a measure of how images are amenable with respect to a given downstream task, or task amenability. When the task is performed using machine learning algorithms, such as a neural-network-based task predictor for image classification or segmentation, the performance of the task predictor provides an objective estimate of task amenability. In this work, we use an IQA controller to predict the task amenability which, itself being parameterised by neural networks, can be trained simultaneously with the task predictor. We further develop a meta-reinforcement learning framework to improve the adaptability for both IQA controllers and task predictors, such that they can be fine-tuned efficiently on new datasets or meta-tasks. We demonstrate the efficacy of the proposed task-specific, adaptable IQA approach, using two clinical applications for ultrasound-guided prostate intervention and pneumonia detection on X-ray images.
View details for DOI 10.1016/j.media.2022.102427
View details for PubMedID 35344824
- The Learn2Reg 2021 MICCAI Grand Challenge (PIMed Team) SPRINGER INTERNATIONAL PUBLISHING AG. 2022: 168-173
EXTERNAL VALIDATION OF AN ARTIFICIAL INTELLIGENCE ALGORITHM FOR PROSTATE CANCER GLEASON GRADING AND TUMOR QUANTIFICATION
LIPPINCOTT WILLIAMS & WILKINS. 2021: E1004
View details for Web of Science ID 000693689000506
Deep Learning Improves Speed and Accuracy of Prostate Gland Segmentations on Magnetic Resonance Imaging for Targeted Biopsy
JOURNAL OF UROLOGY
2021; 206 (3): 605-612
View details for Web of Science ID 000711819100035
DETAILED ANALYSIS OF MRI CONCORDANCE WITH PROSTATECTOMY HISTOPATHOLOGY USING DEEP LEARNING-BASED DIGITAL PATHOLOGY
LIPPINCOTT WILLIAMS & WILKINS. 2021: E813-E814
View details for Web of Science ID 000693689000126
The stanford prostate cancer calculator: Development and external validation of online nomograms incorporating PIRADS scores to predict clinically significant prostate cancer.
BACKGROUND: While multiparametric MRI (mpMRI) has high sensitivity for detection of clinically significant prostate cancer (CSC), false positives and negatives remain common. Calculators that combine mpMRI with clinical variables can improve cancer risk assessment, while providing more accurate predictions for individual patients. We sought to create and externally validate nomograms incorporating Prostate Imaging Reporting and Data System (PIRADS) scores and clinical data to predict the presence of CSC in men of all biopsy backgrounds.METHODS: Data from 2125 men undergoing mpMRI and MR fusion biopsy from 2014 to 2018 at Stanford, Yale, and UAB were prospectively collected. Clinical data included age, race, PSA, biopsy status, PIRADS scores, and prostate volume. A nomogram predicting detection of CSC on targeted or systematic biopsy was created.RESULTS: Biopsy history, Prostate Specific Antigen (PSA) density, PIRADS score of 4 or 5, Caucasian race, and age were significant independent predictors. Our nomogram-the Stanford Prostate Cancer Calculator (SPCC)-combined these factors in a logistic regression to provide stronger predictive accuracy than PSA density or PIRADS alone. Validation of the SPCC using data from Yale and UAB yielded robust AUC values.CONCLUSIONS: The SPCC combines pre-biopsy mpMRI with clinical data to more accurately predict the probability of CSC in men of all biopsy backgrounds. The SPCC demonstrates strong external generalizability with successful validation in two separate institutions. The calculator is available as a free web-based tool that can direct real-time clinical decision-making.
View details for DOI 10.1016/j.urolonc.2021.06.004
View details for PubMedID 34247909
Deep Learning Improves Speed and Accuracy of Prostate Gland Segmentations on MRI for Targeted Biopsy.
The Journal of urology
PURPOSE: Targeted biopsy improves prostate cancer diagnosis. Accurate prostate segmentation on MRI is critical for accurate biopsy. Manual gland segmentation is tedious and time-consuming. We sought to develop a deep learning model to rapidly and accurately segment the prostate on MRI and to implement it as part of routine MR-US fusion biopsy in the clinic.MATERIALS AND METHODS: 905 subjects underwent multiparametric MRI at 29 institutions, followed by MR-US fusion biopsy at one institution. A urologic oncology expert segmented the prostate on axial T2-weighted MRI scans. We trained a deep learning model, ProGNet, on 805 cases. We retrospectively tested ProGNet on 100 independent internal and 56 external cases. We prospectively implemented ProGNet as part of the fusion biopsy procedure for 11 patients. We compared ProGNet performance to two deep learning networks (U-Net and HED) and radiology technicians. The Dice similarity coefficient (DSC) was used to measure overlap with expert segmentations. DSCs were compared using paired t-tests.RESULTS: ProGNet (DSC=0.92) outperformed U-Net (DSC=0.85, p <0.0001), HED (DSC=0.80, p< 0.0001), and radiology technicians (DSC=0.89, p <0.0001) in the retrospective internal test set. In the prospective cohort, ProGNet (DSC=0.93) outperformed radiology technicians (DSC=0.90, p <0.0001). ProGNet took just 35 seconds per case (vs. 10 minutes for radiology technicians) to yield a clinically utilizable segmentation file.CONCLUSIONS: This is the first study to employ a deep learning model for prostate gland segmentation for targeted biopsy in routine urologic clinical practice, while reporting results and releasing the code online. Prospective and retrospective evaluations revealed increased speed and accuracy.
View details for DOI 10.1097/JU.0000000000001783
View details for PubMedID 33878887
Automated Detection of Aggressive and Indolent Prostate Cancer on Magnetic Resonance Imaging.
PURPOSE: While multi-parametric Magnetic Resonance Imaging (MRI) shows great promise in assisting with prostate cancer diagnosis and localization, subtle differences in appearance between cancer and normal tissue lead to many false positive and false negative interpretations by radiologists. We sought to automatically detect aggressive cancer (Gleason pattern ≥ 4) and indolent cancer (Gleason pattern 3) on a per-pixel basis on MRI to facilitate the targeting of aggressive cancer during biopsy.METHODS: We created the Stanford Prostate Cancer Network (SPCNet), a convolutional neural network model, trained to distinguish between aggressive cancer, indolent cancer, and normal tissue on MRI. Ground truth cancer labels were obtainedby registering MRI with whole-mount digital histopathology images from patients that underwent radical prostatectomy. Before registration, these histopathology images were automatically annotated to show Gleason patterns on a per-pixel basis. The model was trained on data from 78 patients that underwent radical prostatectomy and 24 patients without prostate cancer. The model was evaluated on a pixel and lesion level in 322 patients, including: 6 patients with normal MRI and no cancer, 23 patients that underwent radical prostatectomy, and 293 patients that underwent biopsy. Moreover, we assessed the ability of our model to detect clinically significant cancer (lesions with an aggressive component) and compared it to the performance of radiologists.RESULTS: Our model detected clinically significant lesions with an Area Under the Receiver Operator Characteristics Curve of 0.75 for radical prostatectomy patients and 0.80 for biopsy patients. Moreover, the model detected up to 18% of lesions missed by radiologists, and overall had a sensitivity and specificity that approached that of radiologists in detecting clinically significant cancer.CONCLUSIONS: Our SPCNet model accurately detected aggressive prostate cancer. Its performance approached that of radiologists, and it helped identify lesions otherwise missed by radiologists. Our model has the potential to assist physicians in specifically targeting the aggressive component of prostate cancers during biopsy or focal treatment.
View details for DOI 10.1002/mp.14855
View details for PubMedID 33760269
MR method for measuring microscopic histologic soft tissue textures.
Magnetic resonance in medicine
PURPOSE: Provide a direct, non-invasive diagnostic measure of microscopic tissue texture in the size scale between tens of microns and the much larger scale measurable by clinical imaging. This paper presents a method and data demonstrating the ability to measure these microscopic pathologic tissue textures (histology) in the presence of subject motion in an MR scanner. This size range is vital to diagnosing a wide range of diseases.THEORY/METHODS: MR micro-Texture (MRT) resolves these textures by a combination of measuring a targeted set of k-values to characterize texture-as in diffraction analysis of materials, performing a selective internal excitation to isolate a volume of interest (VOI), applying a high k-value phase encode to the excited spins in the VOI, and acquiring each individual k-value data point in a single excitation-providing motion immunity and extended acquisition time for maximizing signal-to-noise ratio. Additional k-value measurements from the same tissue can be made to characterize the tissue texture in the VOI-there is no need for these additional measurements to be spatially coherent as there is no image to be reconstructed. This method was applied to phantoms and tissue specimens including human prostate tissue.RESULTS: Data demonstrating resolution <50 m, motion immunity, and clearly differentiating between normal and cancerous tissue textures are presented.CONCLUSION: The data reveal textural differences not resolvable by standard MR imaging. As MRT is a pulse sequence, it is directly translatable to MRI scanners currently in clinical practice to meet the need for further improvement in cancer imaging.
View details for DOI 10.1002/mrm.28731
View details for PubMedID 33608954
3D Registration of pre-surgical prostate MRI and histopathology images via super-resolution volume reconstruction.
Medical image analysis
2021; 69: 101957
The use of MRI for prostate cancer diagnosis and treatment is increasing rapidly. However, identifying the presence and extent of cancer on MRI remains challenging, leading to high variability in detection even among expert radiologists. Improvement in cancer detection on MRI is essential to reducing this variability and maximizing the clinical utility of MRI. To date, such improvement has been limited by the lack of accurately labeled MRI datasets. Data from patients who underwent radical prostatectomy enables the spatial alignment of digitized histopathology images of the resected prostate with corresponding pre-surgical MRI. This alignment facilitates the delineation of detailed cancer labels on MRI via the projection of cancer from histopathology images onto MRI. We introduce a framework that performs 3D registration of whole-mount histopathology images to pre-surgical MRI in three steps. First, we developed a novel multi-image super-resolution generative adversarial network (miSRGAN), which learns information useful for 3D registration by producing a reconstructed 3D MRI. Second, we trained the network to learn information between histopathology slices to facilitate the application of 3D registration methods. Third, we registered the reconstructed 3D histopathology volumes to the reconstructed 3D MRI, mapping the extent of cancer from histopathology images onto MRI without the need for slice-to-slice correspondence. When compared to interpolation methods, our super-resolution reconstruction resulted in the highest PSNR relative to clinical 3D MRI (32.15 dB vs 30.16 dB for BSpline interpolation). Moreover, the registration of 3D volumes reconstructed via super-resolution for both MRI and histopathology images showed the best alignment of cancer regions when compared to (1) the state-of-the-art RAPSODI approach, (2) volumes that were not reconstructed, or (3) volumes that were reconstructed using nearest neighbor, linear, or BSpline interpolations. The improved 3D alignment of histopathology images and MRI facilitates the projection of accurate cancer labels on MRI, allowing for the development of improved MRI interpretation schemes and machine learning models to automatically detect cancer on MRI.
View details for DOI 10.1016/j.media.2021.101957
View details for PubMedID 33550008
Optimization of a Thermal Flow Meter for Failure Management of the Shunt in Pediatric Hydrocephalus Patients.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
2021; 2021: 1551-1556
Hydrocephalus patients suffer from an abnormal buildup of cerebrospinal fluid (CSF) in their ventricles, and there is currently no known way to cure hydrocephalus. The most prevalent treatment for managing hydrocephalus is to implant a ventriculoperitoneal shunt, which diverts excess CSF out of the brain. However, shunts are prone to failure, resulting in vague symptoms. Our patient survey results found that the lack of specificity of symptoms complicates the management of hydrocephalus in the pediatric population. The consequences include persistent mental burden on caretakers and a significant amount of unnecessary utilization of emergency healthcare resources due to the false-positive judgement of shunt failure. In order to reliably monitor shunt failures for hydrocephalus patients and their caretakers, we propose an optimized design of the thermal flow meter for precise measurements of the CSF flow rate in the shunt. The design is an implantable device which slides onto the shunt and utilizes sinusoidal heating and temperature measurements to improve the signal-to-noise ratio of flow-rate measurements by orders of magnitude.Clinical Relevance- An implantable flow meter would be transformative to allow hydrocephalus patients to monitor their shunt function at home, resulting in reduced hospital visits, reduced exposure to radiation typically required to rule out shunt failure, and reduced caretaker anxiety.
View details for DOI 10.1109/EMBC46164.2021.9630302
View details for PubMedID 34891580
- ProGNet: Prostate Gland Segmentation on MRI with Deep Learning SPIE-INT SOC OPTICAL ENGINEERING. 2021
Selective identification and localization of indolent and aggressive prostate cancers via CorrSigNIA: an MRI-pathology correlation and deep learning framework.
Medical image analysis
2021; 75: 102288
Automated methods for detecting prostate cancer and distinguishing indolent from aggressive disease on Magnetic Resonance Imaging (MRI) could assist in early diagnosis and treatment planning. Existing automated methods of prostate cancer detection mostly rely on ground truth labels with limited accuracy, ignore disease pathology characteristics observed on resected tissue, and cannot selectively identify aggressive (Gleason Pattern≥4) and indolent (Gleason Pattern=3) cancers when they co-exist in mixed lesions. In this paper, we present a radiology-pathology fusion approach, CorrSigNIA, for the selective identification and localization of indolent and aggressive prostate cancer on MRI. CorrSigNIA uses registered MRI and whole-mount histopathology images from radical prostatectomy patients to derive accurate ground truth labels and learn correlated features between radiology and pathology images. These correlated features are then used in a convolutional neural network architecture to detect and localize normal tissue, indolent cancer, and aggressive cancer on prostate MRI. CorrSigNIA was trained and validated on a dataset of 98 men, including 74 men that underwent radical prostatectomy and 24 men with normal prostate MRI. CorrSigNIA was tested on three independent test sets including 55 men that underwent radical prostatectomy, 275 men that underwent targeted biopsies, and 15 men with normal prostate MRI. CorrSigNIA achieved an accuracy of 80% in distinguishing between men with and without cancer, a lesion-level ROC-AUC of 0.81±0.31 in detecting cancers in both radical prostatectomy and biopsy cohort patients, and lesion-levels ROC-AUCs of 0.82±0.31 and 0.86±0.26 in detecting clinically significant cancers in radical prostatectomy and biopsy cohort patients respectively. CorrSigNIA consistently outperformed other methods across different evaluation metrics and cohorts. In clinical settings, CorrSigNIA may be used in prostate cancer detection as well as in selective identification of indolent and aggressive components of prostate cancer, thereby improving prostate cancer care by helping guide targeted biopsies, reducing unnecessary biopsies, and selecting and planning treatment.
View details for DOI 10.1016/j.media.2021.102288
View details for PubMedID 34784540
- Weakly Supervised Registration of Prostate MRI and Histopathology Images SPRINGER INTERNATIONAL PUBLISHING AG. 2021: 98-107
UTILITY OF PSA DENSITY IN PREDICTING UPGRADED GLEASON SCORE IN MEN ON ACTIVE SURVEILLANCE WITH NEGATIVE MRI.
To determine whether PSA density (PSAD), can sub-stratify risk of biopsy upgrade among men on active surveillance (AS) with normal baseline MRI.We identified a cohort of patients with low and favorable intermediate-risk prostate cancer on AS at two large academic centers from February 2013 - December 2017. Analysis was restricted to patients with GG1 cancer on initial biopsy and a negative baseline or surveillance mpMRI, defined by the absence of PI-RADS 2 or greater lesions. We assessed ability of PSA, prostate volume and PSAD to predict upgrading on confirmatory biopsy.We identified 98 patients on AS with negative baseline or surveillance mpMRI. Median PSA at diagnosis was 5.8 ng/mL and median PSAD was 0.08 ng/mL/mL. Fourteen men (14.3%) experienced Gleason upgrade at confirmatory biopsy. Patients who were upgraded had higher PSA (7.9 vs. 5.4 ng/mL, p=0.04), PSAD (0.20 vs. 0.07 ng/mL/mL, p<0.001), and lower prostate volumes (42.5 vs. 65.8 mL, p=0.01). On multivariate analysis, PSAD was associated with pathologic upgrade (OR 2.23 per 0.1-increase, p=0.007). A PSAD cutoff at 0.08 generated a NPV of 98% for detection of pathologic upgrade.PSAD reliably discriminated the risk of Gleason upgrade at confirmatory biopsy among men with low-grade prostate cancer with negative MRI. PSAD could be clinically implemented to reduce the intensity of surveillance for a subset of patients.
View details for DOI 10.1016/j.urology.2021.05.035
View details for PubMedID 34087311
- Adaptable Image Quality Assessment Using Meta-Reinforcement Learning of Task Amenability SPRINGER INTERNATIONAL PUBLISHING AG. 2021: 191-201
- Clinically significant prostate cancer detection on MRI with self-supervised learning using image context restoration SPIE-INT SOC OPTICAL ENGINEERING. 2021
Clinical -Prostate cancer Multicenter analysis of clinical and MRI characteristics associated with detecting clinically significant prostate cancer in PI-RADS (v2.0) category 3 lesions
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
2020; 38 (7)
View details for Web of Science ID 000542437900009
Registration of pre-surgical MRI and histopathology images from radical prostatectomy via RAPSODI.
PURPOSE: Magnetic resonance imaging (MRI) has great potential to improve prostate cancer diagnosis, however, subtle differences between cancer and confounding conditions render prostate MRI interpretation challenging. The tissue collected from patients who undergo radical prostatectomy provides a unique opportunity to correlate histopathology images of the prostate with pre-operative MRI to accurately map the extent of cancer from histopathology images onto MRI. We seek to develop an open-source, easy-to-use platform to align pre-surgical MRI and histopathology images of resected prostates in patients who underwent radical prostatectomy to create accurate cancer labels on MRI.METHODS: Here, we introduce RAdiology Pathology Spatial Open-Source multi-Dimensional Integration (RAPSODI), the first open-source framework for the registration of radiology and pathology images. RAPSODI relies on three steps. First, it creates a 3D reconstruction of the histopathology specimen as a digital representation of the tissue before gross sectioning. Second, RAPSODI registers corresponding histopathology and MRI slices. Third, the optimized transforms are applied to the cancer regions outlined on the histopathology images to project those labels onto the pre-operative MRI.RESULTS: We tested RAPSODI in a phantom study where we simulated various conditions, e.g., tissue shrinkage during fixation. Our experiments showed that RAPSODI can reliably correct multiple artifacts. We also evaluated RAPSODI in 157 patients from three institutions that underwent radical prostatectomy and have very different pathology processing and scanning. RAPSODI was evaluated in 907 corresponding histpathology-MRI slices and achieved a Dice coefficient of 0.97±0.01 for the prostate, a Hausdorff distance of 1.99±0.70 mm for the prostate boundary, a urethra deviation of 3.09±1.45 mm, and a landmark deviation of 2.80±0.59 mm between registered histopathology images and MRI.CONCLUSION: Our robust framework successfully mapped the extent of cancer from histopathology slices onto MRI providing labels from training machine learning methods to detect cancer on MRI.
View details for DOI 10.1002/mp.14337
View details for PubMedID 32564359
ProsRegNet: A deep learning framework for registration of MRI and histopathology images of the prostate.
Medical image analysis
2020; 68: 101919
Magnetic resonance imaging (MRI) is an increasingly important tool for the diagnosis and treatment of prostate cancer. However, interpretation of MRI suffers from high inter-observer variability across radiologists, thereby contributing to missed clinically significant cancers, overdiagnosed low-risk cancers, and frequent false positives. Interpretation of MRI could be greatly improved by providing radiologists with an answer key that clearly shows cancer locations on MRI. Registration of histopathology images from patients who had radical prostatectomy to pre-operative MRI allows such mapping of ground truth cancer labels onto MRI. However, traditional MRI-histopathology registration approaches are computationally expensive and require careful choices of the cost function and registration hyperparameters. This paper presents ProsRegNet, a deep learning-based pipeline to accelerate and simplify MRI-histopathology image registration in prostate cancer. Our pipeline consists of image preprocessing, estimation of affine and deformable transformations by deep neural networks, and mapping cancer labels from histopathology images onto MRI using estimated transformations. We trained our neural network using MR and histopathology images of 99 patients from our internal cohort (Cohort 1) and evaluated its performance using 53 patients from three different cohorts (an additional 12 from Cohort 1 and 41 from two public cohorts). Results show that our deep learning pipeline has achieved more accurate registration results and is at least 20 times faster than a state-of-the-art registration algorithm. This important advance will provide radiologists with highly accurate prostate MRI answer keys, thereby facilitating improvements in the detection of prostate cancer on MRI. Our code is freely available at https://github.com/pimed//ProsRegNet.
View details for DOI 10.1016/j.media.2020.101919
View details for PubMedID 33385701
Multicenter analysis of clinical and MRI characteristics associated with detecting clinically significant prostate cancer in PI-RADS (v2.0) category 3 lesions.
We sought to identify clinical and magnetic resonance imaging (MRI) characteristics in men with the Prostate Imaging - Reporting and Data System (PI-RADS) category 3 index lesions that predict clinically significant prostate cancer (CaP) on MRI targeted biopsy.Multicenter study of prospectively collected data for biopsy-naive men (n = 247) who underwent MRI-targeted and systematic biopsies for PI-RADS 3 index lesions. The primary endpoint was diagnosis of clinically significant CaP (Grade Group ≥2). Multivariable logistic regression models assessed for factors associated with clinically significant CaP. The probability distributions of clinically significant CaP based on different levels of predictors of multivariable models were plotted in a heatmap.Men with clinically significant CaP had smaller prostate volume (39.20 vs. 55.10 ml, P < 0.001) and lower apparent diffusion coefficient (ADC) values (973 vs. 1068 μm2/s, P = 0.013), but higher prostate-specific antigen (PSA) density (0.21 vs. 0.13 ng/ml2, P = 0.027). On multivariable analyses, lower prostate volume (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.92-0.97), lower ADC value (OR: 0.99, 95% CI: 0.99-1.00), and Prostate-specific antigen density >0.15 ng/ml2 (OR: 3.51, 95% CI 1.61-7.68) were independently associated with significant CaP.Higher PSA density, lower prostate volume and ADC values are associated with clinically significant CaP in biopsy-naïve men with PI-RADS 3 lesions. We present regression-derived probabilities of detecting clinically significant CaP based on various clinical and imaging values that can be used in decision-making. Our findings demonstrate an opportunity for MRI refinement or biomarker discovery to improve risk stratification for PI-RADS 3 lesions.
View details for DOI 10.1016/j.urolonc.2020.03.019
View details for PubMedID 32307327
Simultaneous transrectal ultrasound and photoacoustic human prostate imaging.
Science translational medicine
2019; 11 (507)
Imaging technologies that simultaneously provide anatomical, functional, and molecular information are emerging as an attractive choice for disease screening and management. Since the 1980s, transrectal ultrasound (TRUS) has been routinely used to visualize prostatic anatomy and guide needle biopsy, despite limited specificity. Photoacoustic imaging (PAI) provides functional and molecular information at ultrasonic resolution based on optical absorption. Combining the strengths of TRUS and PAI approaches, we report the development and bench-to-bedside translation of an integrated TRUS and photoacoustic (TRUSPA) device. TRUSPA uses a miniaturized capacitive micromachined ultrasonic transducer array for simultaneous imaging of anatomical and molecular optical contrasts [intrinsic: hemoglobin; extrinsic: intravenous indocyanine green (ICG)] of the human prostate. Hemoglobin absorption mapped vascularity of the prostate and surroundings, whereas ICG absorption enhanced the intraprostatic photoacoustic contrast. Future work using the TRUSPA device for biomarker-specific molecular imaging may enable a fundamentally new approach to prostate cancer diagnosis, prognostication, and therapeutic monitoring.
View details for DOI 10.1126/scitranslmed.aav2169
View details for PubMedID 31462508
- Prostate Magnetic Resonance Imaging Interpretation Varies Substantially Across Radiologists EUROPEAN UROLOGY FOCUS 2019; 5 (4): 592–99
How Often is the Dynamic Contrast Enhanced Score Needed in PI-RADS Version 2?
Current problems in diagnostic radiology
BACKGROUND: Prostate imaging reporting and data system version 2 (PI-RADS v2) relegates dynamic contrast enhanced (DCE) imaging to a minor role. We sought to determine how often DCE is used in PI-RADS v2 scoring.MATERIALS AND METHODS: We retrospectively reviewed data from 388 patients who underwent prostate magnetic resonance imaging and subsequent biopsy from January 2016 through December 2017. In accordance with PI-RADS v2, DCE was deemed necessary if a peripheral-zone lesion had a diffusion-weighted imaging score of 3, or if a transition-zone lesion had a T2 score of 3 and diffusion-weighted imaging experienced technical failure. Receiver operating characteristic curve analysis assessed the accuracy of prostate-specific antigen density (PSAD) at different threshold values for differentiating lesions that would be equivocal with noncontrast technique. Accuracy of PSAD was compared to DCE using McNemar's test.RESULTS: Sixty-nine lesions in 62 patients (16%) required DCE for PI-RADS scoring. Biopsy of 10 (14%) of these lesions showed clinically significant cancer (Gleason score ≥7). In the subgroup of patients with equivocal lesions, those with clinically significant cancer had significantly higher PSADs than those with clinically insignificant lesions (means of 0.18 and 0.13 ng/mL/mL, respectively; P= 0.038). In this subgroup, there was no statistical difference in accuracy in determining clinically significant cancer between a PSAD threshold value of 0.13 and DCE (P= 0.25).CONCLUSIONS: Only 16% of our patients needed DCE to generate the PI-RADS version 2 score, raising the possibility of limiting the initial screening prostate MRI to a noncontrast exam. PSAD may also be used to further decrease the need for or to replace DCE altogether.
View details for DOI 10.1067/j.cpradiol.2019.05.008
View details for PubMedID 31126664
AUTOMATED DETECTION OF PROSTATE CANCER ON MULTIPARAMETRIC MRI USING DEEP NEURAL NETWORKS TRAINED ON SPATIAL COORDINATES AND PATHOLOGY OF BIOPSY CORES
LIPPINCOTT WILLIAMS & WILKINS. 2019: E1098
View details for Web of Science ID 000473345203470
GENERALIZABLE MULTI-SITE TRAINING AND TESTING OF DEEP NEURAL NETWORKS USING IMAGE NORMALIZATION.
Proceedings. IEEE International Symposium on Biomedical Imaging
2019; 2019: 348-351
The ability of medical image analysis deep learning algorithms to generalize across multiple sites is critical for clinical adoption of these methods. Medical imging data, especially MRI, can have highly variable intensity characteristics across different individuals, scanners, and sites. However, it is not practical to train algorithms with data from all imaging equipment sources at all possible sites. Intensity normalization methods offer a potential solution for working with multi-site data. We evaluate five different image normalization methods on training a deep neural network to segment the prostate gland in MRI. Using 600 MRI prostate gland segmentations from two different sites, our results show that both intra-site and inter-site evaluation is critical for assessing the robustness of trained models and that training with single-site data produces models that fail to fully generalize across testing data from sites not included in the training.
View details for DOI 10.1109/isbi.2019.8759295
View details for PubMedID 32874427
View details for PubMedCentralID PMC7457546
Applying the PRECISION approach in biopsy naïve and previously negative prostate biopsy patients.
The PRECISION trial provides level 1 evidence supporting prebiopsy multiparametric magnetic resonance imaging (mpMRI) followed by targeted biopsy only when mpMRI is abnormal . This approach reduced over-detection of low-grade cancer while increasing detection of clinically significant cancer (CSC). Still, important questions remain regarding the reproducibility of these findings outside of a clinical trial and quantifying missed CSC diagnoses using this approach. To address these issues, we retrospectively applied the PRECISION strategy in men who each underwent prebiopsy mpMRI followed by systematic and targeted biopsy.Clinical, imaging, and pathology data were prospectively collected from 358 biopsy naïve men and 202 men with previous negative biopsies. To apply the PRECISION approach, a retrospective analysis was done comparing the cancer yield from 2 diagnostic strategies: (1) mpMRI followed by targeted biopsy alone for men with Prostate Imaging Reporting and Data System ≥ 3 lesions and (2) systematic biopsy alone for all men. Primary outcomes were biopsies avoided and the proportion of CSC cancer (Grade Group 2-5) and non-CSC (Grade Group 1).In biopsy naïve patients, the mpMRI diagnostic strategy would have avoided 19% of biopsies while detecting 2.5% more CSC (P= 0.480) and 12% less non-CSC (P< 0.001). Thirteen percent (n= 9) of men with normal mpMRI had CSC on systematic biopsy. For previous negative biopsy patients, the mpMRI diagnostic strategy avoided 21% of biopsies, while detecting 1.5% more CSC (P= 0.737) and 13% less non-CSC (P< 0.001). Seven percent (n= 3) of men with normal mpMRI had CSC on systematic biopsy.Our results provide external validation of the PRECISION finding that mpMRI followed by targeted biopsy of suspicious lesions reduces biopsies and over-diagnosis of low-grade cancer. Unlike PRECISION, we did not find increased diagnosis of CSC. This was true in both biopsy naïve and previously negative biopsy cohorts. We have incorporated this information into shared decision making, which has led some men to choose to avoid biopsy. However, we continue to recommend targeted and systematic biopsy in men with abnormal MRI.
View details for DOI 10.1016/j.urolonc.2019.05.002
View details for PubMedID 31151788
GENERALIZABLE MULTI-SITE TRAINING AND TESTING OF DEEP NEURAL NETWORKS USING IMAGE NORMALIZATION
IEEE. 2019: 348–51
View details for Web of Science ID 000485040000074
- Framework for the co-registration of MRI and Histology Images in Prostate Cancer Patients with Radical Prostatectomy SPIE-INT SOC OPTICAL ENGINEERING. 2019
Teaching Urologists "How to Read Multi-Parametric Prostate MRIs Using PIRADSv2": Results of an iBook Pilot Study.
To create an online resource that teaches urologists how to interpret prostate multi-parametric MRIs (mpMRI). As prostate mpMRI becomes widely adopted for cancer diagnosis and targeted biopsy, it is increasingly important that urologists are comfortable and experienced in assessing the images. The purpose of this study was to create an online mpMRI ibook and measure its effect on instilling proficiency amongst urology residents.We created a case-based ibook aimed at teaching clinicians how to identify and score prostate lesions on mpMRI using the Prostate Imaging and Reporting Data System (PIRADS) v2. Residents completed a 43-question pre-test before gaining access to the ibook for one month. The test asks participants to identify and score visible lesions using interactive mpMRI images. After a formal review of the material, they completed a post-test. Participants also rated their diagnostic confidence on a scale of 1 to 10 before and after reviewing the ibook. The change in performance and confidence scores for each resident was compared using Wilcoxon Signed-Rank test.Eleven urology residents completed the pre-test, review session and post-test. The mean test score rose from 37% (median 40%) to 57% (median 58%) after reviewing the ibook. Improvement was significant (p=0.0039). Confidence scores also improved (p=0.001).We created an interactive ibook that teaches urologists how to evaluate prostate mpMRIs and demonstrated improved performance in interpretation amongst urology residents. This effective module can be incorporated into resident education on a national level and offered as a self-teaching resource for practicing urologists.
View details for DOI 10.1016/j.urology.2019.04.040
View details for PubMedID 31150691
Performance of multiparametric MRI appears better when measured in patients who undergo radical prostatectomy.
Research and reports in urology
2018; 10: 233-235
Utilization of pre-biopsy multiparametric MRI (mpMRI) is increasing. To optimize the usefulness of mpMRI, physicians should accurately quote patients a numerical risk of cancer based on their MRI. The Prostate Imaging Reporting and Data System (PIRADS) standardizes interpretation of mpMRI; however, reported rates of clinically significant prostate cancer (CSC) stratified by PIRADS score vary widely. While some publications use radical prostatectomy (RP) specimens as gold standard, others use biopsy. We hypothesized that much of the variation in CSC stems from differences in cancer prevalence in RP cohorts (100% prevalence) vs biopsy cohorts. To quantify the impact of this selection bias on cancer yield according to PIRADS score, we analyzed data from 614 men with 854 lesions who underwent targeted biopsy from 2014 to 2018. Of these, 125 men underwent RP. We compared the PIRADS detection rates of CSC (Gleason ≥7) on targeted biopsy between the biopsy-only and RP cohorts. For all PIRADS scores, CSC yield was much greater in patients who underwent RP. For example, CSC was found in 30% of PIRADS 3 lesions in men who underwent RP vs 7.6% in men who underwent biopsy. Our results show that mpMRI performance appears to be better in men who undergo RP compared with those who only receive biopsy. Physicians should understand the effect of this selection bias and its magnitude when discussing mpMRI results with patients considering biopsy, and take great caution in quoting CSC yields from publications using RP as gold standard.
View details for DOI 10.2147/RRU.S178064
View details for PubMedID 30538970
View details for PubMedCentralID PMC6254536
- Gallium 68 PSMA-11 PET/MR Imaging in Patients with Intermediate- or High-Risk Prostate Cancer RADIOLOGY 2018; 288 (2): 495–505
- Reduction of Muscle Contractions during Irreversible Electroporation Therapy Using High-Frequency Bursts of Alternating Polarity Pulses: A Laboratory Investigation in an Ex Vivo Swine Model JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY 2018; 29 (6): 893–98
Gallium 68 PSMA-11 PET/MR Imaging in Patients with Intermediate- or High-Risk Prostate Cancer.
Purpose To report the results of dual-time-point gallium 68 (68Ga) prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/magnetic resonance (MR) imaging prior to prostatectomy in patients with intermediate- or high-risk cancer. Materials and Methods Thirty-three men who underwent conventional imaging as clinically indicated and who were scheduled for radical prostatectomy with pelvic lymph node dissection were recruited for this study. A mean dose of 4.1 mCi ± 0.7 (151.7 MBq ± 25.9) of 68Ga-PSMA-11 was administered. Whole-body images were acquired starting 41-61 minutes after injection by using a GE SIGNA PET/MR imaging unit, followed by an additional pelvic PET/MR imaging acquisition at 87-125 minutes after injection. PET/MR imaging findings were compared with findings at multiparametric MR imaging (including diffusion-weighted imaging, T2-weighted imaging, and dynamic contrast material-enhanced imaging) and were correlated with results of final whole-mount pathologic examination and pelvic nodal dissection to yield sensitivity and specificity. Dual-time-point metabolic parameters (eg, maximum standardized uptake value [SUVmax]) were compared by using a paired t test and were correlated with clinical and histopathologic variables including prostate-specific antigen level, Gleason score, and tumor volume. Results Prostate cancer was seen at 68Ga-PSMA-11 PET in all 33 patients, whereas multiparametric MR imaging depicted Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesions in 26 patients and PI-RADS 3 lesions in four patients. Focal uptake was seen in the pelvic lymph nodes in five patients. Pathologic examination confirmed prostate cancer in all patients, as well as nodal metastasis in three. All patients with normal pelvic nodes in PET/MR imaging had no metastases at pathologic examination. The accumulation of 68Ga-PSMA-11 increased at later acquisition times, with higher mean SUVmax (15.3 vs 12.3, P < .001). One additional prostate cancer was identified only at delayed imaging. Conclusion This study found that 68Ga-PSMA-11 PET can be used to identify prostate cancer, while MR imaging provides detailed anatomic guidance. Hence, 68Ga-PSMA-11 PET/MR imaging provides valuable diagnostic information and may inform the need for and extent of pelvic node dissection.
View details for PubMedID 29786490
The impact of computed high b-value images on the diagnostic accuracy of DWI for prostate cancer: A receiver operating characteristics analysis.
2018; 8 (1): 3409
To evaluate the performance of computed high b value diffusion-weighted images (DWI) in prostate cancer detection. 97 consecutive patients who had undergone multiparametric MRI of the prostate followed by biopsy were reviewed. Five radiologists independently scored 138 lesions on native high b-value images (b = 1200 s/mm2), apparent diffusion coefficient (ADC) maps, and computed high b-value images (contrast equivalent to b = 2000 s/mm2) to compare their diagnostic accuracy. Receiver operating characteristic (ROC) analysis and McNemar's test were performed to assess the relative performance of computed high b value DWI, native high b-value DWI and ADC maps. No significant difference existed in the area under the curve (AUC) for ROCs comparing B1200 (b = 1200 s/mm2) to computed B2000 (c-B2000) in 5 readers. In 4 of 5 readers c-B2000 had significantly increased sensitivity and/or decreased specificity compared to B1200 (McNemar's p < 0.05), at selected thresholds of interpretation. ADC maps were less accurate than B1200 or c-B2000 for 2 of 5 readers (P < 0.05). This study detected no consistent improvement in overall diagnostic accuracy using c-B2000, compared with B1200 images. Readers detected more cancer with c-B2000 images (increased sensitivity) but also more false positive findings (decreased specificity).
View details for PubMedID 29467370
- Performance of multiparametric MRI appears better when measured in patients who undergo radical prostatectomy RESEARCH AND REPORTS IN UROLOGY 2018; 10: 233–35
Reduction of Muscle Contractions during Irreversible Electroporation Therapy Using High-Frequency Bursts of Alternating Polarity Pulses: A Laboratory Investigation in an ExVivo Swine Model.
Journal of vascular and interventional radiology : JVIR
2018; 29 (6): 893
PURPOSE: To compare the intensity of muscle contractions in irreversible electroporation (IRE) treatments when traditional IRE and high-frequency IRE (H-FIRE) waveforms are used in combination with a single applicator and distal grounding pad (A+GP) configuration.MATERIALS AND METHODS: An exvivo in situ porcine model was used to compare muscle contractions induced by traditional monopolar IRE waveforms vs high-frequency bipolar IRE waveforms. Pulses with voltages between 200 and 5,000 V were investigated, and muscle contractions were recorded by using accelerometers placed on or near the applicators.RESULTS: H-FIRE waveforms reduced the intensity of muscle contractions in comparison with traditional monopolar IRE pulses. A high-energy burst of 2-mus alternating-polarity pulses energized for 200 mus at 4,500 V produced less intense muscle contractions than traditional IRE pulses, which were 25-100 mus in duration at 3,000 V.CONCLUSIONS: H-FIRE appears to be an effective technique to mitigate the muscle contractions associated with traditional IRE pulses. This may enable the use of voltages greater than 3,000 V necessary for the creation of large ablations invivo.
View details for PubMedID 29628296
Mass spectrometric imaging of prostate biopsy samples: Cancer margin assessment from the distribution of small metabolites and lipids
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430568500539
Diagnosis of prostate cancer by desorption electrospray ionization mass spectrometric imaging of small metabolites and lipids
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2017; 114 (13): 3334-3339
Accurate identification of prostate cancer in frozen sections at the time of surgery can be challenging, limiting the surgeon's ability to best determine resection margins during prostatectomy. We performed desorption electrospray ionization mass spectrometry imaging (DESI-MSI) on 54 banked human cancerous and normal prostate tissue specimens to investigate the spatial distribution of a wide variety of small metabolites, carbohydrates, and lipids. In contrast to several previous studies, our method included Krebs cycle intermediates (m/z <200), which we found to be highly informative in distinguishing cancer from benign tissue. Malignant prostate cells showed marked metabolic derangements compared with their benign counterparts. Using the "Least absolute shrinkage and selection operator" (Lasso), we analyzed all metabolites from the DESI-MS data and identified parsimonious sets of metabolic profiles for distinguishing between cancer and normal tissue. In an independent set of samples, we could use these models to classify prostate cancer from benign specimens with nearly 90% accuracy per patient. Based on previous work in prostate cancer showing that glucose levels are high while citrate is low, we found that measurement of the glucose/citrate ion signal ratio accurately predicted cancer when this ratio exceeds 1.0 and normal prostate when the ratio is less than 0.5. After brief tissue preparation, the glucose/citrate ratio can be recorded on a tissue sample in 1 min or less, which is in sharp contrast to the 20 min or more required by histopathological examination of frozen tissue specimens.
View details for DOI 10.1073/pnas.1700677114
View details for Web of Science ID 000397607300049
View details for PubMedID 28292895
View details for PubMedCentralID PMC5380053
Asymmetric Waveforms Decrease Lethal Thresholds in High Frequency Irreversible Electroporation Therapies
Irreversible electroporation (IRE) is a promising non-thermal treatment for inoperable tumors which uses short (50-100 μs) high voltage monopolar pulses to disrupt the membranes of cells within a well-defined volume. Challenges with IRE include complex treatment planning and the induction of intense muscle contractions. High frequency IRE (H-FIRE) uses bursts of ultrashort (0.25-5 μs) alternating polarity pulses to produce more predictable ablations and alleviate muscle contractions associated with IRE. However, H-FIRE generally ablates smaller volumes of tissue than IRE. This study shows that asymmetric H-FIRE waveforms can be used to create ablation volumes equivalent to standard IRE treatments. Lethal thresholds (LT) of 505 V/cm and 1316 V/cm were found for brain cancer cells when 100 μs IRE and 2 μs symmetric H-FIRE waveforms were used. In contrast, LT as low as 536 V/cm were found for 2 μs asymmetric H-FIRE waveforms. Reversible electroporation thresholds were 54% lower than LTs for symmetric waveforms and 33% lower for asymmetric waveforms indicating that waveform symmetry can be used to tune the relative sizes of reversible and irreversible ablation zones. Numerical simulations predicted that asymmetric H-FIRE waveforms are capable of producing ablation volumes which were 5.8-6.3x larger than symmetric H-FIRE waveforms indicating that in vivo investigation of asymmetric waveforms is warranted.
View details for DOI 10.1038/srep40747
View details for Web of Science ID 000392345600001
View details for PubMedID 28106146
View details for PubMedCentralID PMC5247773
Prostate Magnetic Resonance Imaging Interpretation Varies Substantially Across Radiologists.
European urology focus
Multiparametric magnetic resonance imaging (mpMRI) interpreted by experts is a powerful tool for diagnosing prostate cancer. However, the generalizability of published results across radiologists of varying expertise has not been verified.To assess variability in mpMRI reporting and diagnostic accuracy across radiologists of varying experience in routine clinical care.Men who underwent mpMRI and MR-fusion biopsy between 2014-2016. Each MRI scan was read by one of nine radiologists using the Prostate Imaging Reporting and Data System (PIRADS) and was not re-read before biopsy. Biopsy histopathology was the reference standard.Outcomes were the PIRADS score distribution and diagnostic accuracy across nine radiologists. We evaluated the association between age, prostate-specific antigen, PIRADS score, and radiologist in predicting clinically significant cancer (Gleason ≥7) using multivariable logistic regression. We conducted sensitivity analyses for case volume and changes in accuracy over time.We analyzed data for 409 subjects with 503 MRI lesions. While the number of lesions (mean 1.2 lesions/patient) did not differ across radiologists, substantial variation existed in PIRADS distribution and cancer yield. The significant cancer detection rate was 3-27% for PIRADS 3 lesions, 23-65% for PIRADS 4, and 40-80% for PIRADS 5 across radiologists. Some 13-60% of men with a PIRADS score of <3 on MRI harbored clinically significant cancer. The area under the receiver operating characteristic curve varied from 0.69 to 0.81 for detection of clinically significant cancer. PIRADS score (p<0.0001) and radiologist (p=0.042) were independently associated with cancer in multivariable analysis. Neither individual radiologist volume nor study period impacted the results. MRI scans were not retrospectively re-read by all radiologists, precluding measurement of inter-observer agreement.We observed considerable variability in PIRADS score assignment and significant cancer yield across radiologists. We advise internal evaluation of mpMRI accuracy before widespread adoption.We evaluated the interpretation of multiparametric magnetic resonance imaging of the prostate in routine clinical care. Diagnostic accuracy depends on the Prostate Imaging Reporting and Data System score and the radiologist.
View details for PubMedID 29226826
Production of Spherical Ablations Using Nonthermal Irreversible Electroporation: A Laboratory Investigation Using a Single Electrode and Grounding Pad.
Journal of vascular and interventional radiology
2016; 27 (9): 1432-1440 e3
To mathematically model and test ex vivo a modified technique of irreversible electroporation (IRE) to produce large spherical ablations by using a single probe.Computed simulations were performed by using varying voltages, electrode exposure lengths, and tissue types. A vegetable (potato) tissue model was then used to compare ablations created by conventional and high-frequency IRE protocols by using 2 probe configurations: a single probe with two collinear electrodes (2EP) or a single electrode configured with a grounding pad (P+GP). The new P+GP electrode configuration was evaluated in ex vivo liver tissue.The P+GP configuration produced more spherical ablation volumes than the 2EP configuration in computed simulations and tissue models. In prostate tissue, computed simulations predicted ablation volumes at 3,000 V of 1.6 cm(3) for the P+GP configurations, compared with 0.94 cm(3) for the 2EP configuration; in liver tissue, the predicted ablation volumes were 4.7 times larger than those in the prostate. Vegetable model studies verify that the P+GP configuration produces larger and more spherical ablations than those produced by the 2EP. High-frequency IRE treatment of ex vivo liver with the P+GP configuration created a 2.84 × 2.21-cm ablation zone.Computer modeling showed that P+GP configuration for IRE procedures yields ablations that are larger than the 2EP configuration, creating substantial ablation zones with a single electrode placement. When tested in tissue models and an ex vivo liver model, the P+GP configuration created ablation zones that appear to be of clinically relevant size and shape.
View details for DOI 10.1016/j.jvir.2016.05.032
View details for PubMedID 27478129
- PROSTATE CANCER YIELD IN MRI LESIONS VARIES ACROSS RADIOLOGISTS ELSEVIER SCIENCE INC. 2016: E42
- Simplified prostate lesion grading for magnetic resonance imaging and improved cancer detection at fusion-targeted prostate biopsy. AMER SOC CLINICAL ONCOLOGY. 2015
Haptic Biofeedback for Improving Compliance With Lower-Extremity Partial Weight Bearing
2014; 37 (11): E993–E998
After lower-extremity orthopedic trauma and surgery, patients are often advised to restrict weight bearing on the affected limb. Conventional training methods are not effective at enabling patients to comply with recommendations for partial weight bearing. The current study assessed a novel method of using real-time haptic (vibratory/vibrotactile) biofeedback to improve compliance with instructions for partial weight bearing. Thirty healthy, asymptomatic participants were randomized into 1 of 3 groups: verbal instruction, bathroom scale training, and haptic biofeedback. Participants were instructed to restrict lower-extremity weight bearing in a walking boot with crutches to 25 lb, with an acceptable range of 15 to 35 lb. A custom weight bearing sensor and biofeedback system was attached to all participants, but only those in the haptic biofeedback group were given a vibrotactile signal if they exceeded the acceptable range. Weight bearing in all groups was measured with a separate validated commercial system. The verbal instruction group bore an average of 60.3±30.5 lb (mean±standard deviation). The bathroom scale group averaged 43.8±17.2 lb, whereas the haptic biofeedback group averaged 22.4±9.1 lb (P<.05). As a percentage of body weight, the verbal instruction group averaged 40.2±19.3%, the bathroom scale group averaged 32.5±16.9%, and the haptic biofeedback group averaged 14.5±6.3% (P<.05). In this initial evaluation of the use of haptic biofeedback to improve compliance with lower-extremity partial weight bearing, haptic biofeedback was superior to conventional physical therapy methods. Further studies in patients with clinical orthopedic trauma are warranted.
View details for DOI 10.3928/01477447-20141023-56
View details for Web of Science ID 000344972700016
View details for PubMedID 25361376
A Novel Device to Preserve Intestinal Tissue Ex-Vivo by Cold Peristaltic Perfusion
IEEE. 2014: 3118–21
In the past two decades, much advancement has been made in the area of organ procurement and preservation for the transplant of kidneys, livers, and lungs. However, small intestine preservation remains unchanged. We propose a new preservation system for intestinal grafts that has the potential to increase the viability of the organ during transport. When experimented with porcine intestine, our device resulted in superior tissue quality than tissue in standard of care.
View details for Web of Science ID 000350044703028
View details for PubMedID 25570651
The role of tactile feedback in grip force during laparoscopic training tasks
SPRINGER. 2013: 1111–18
Laparoscopic minimally invasive surgery has revolutionized surgical care by reducing trauma to the patient, thereby decreasing the need for medication and shortening recovery times. During open procedures, surgeons can directly feel tissue characteristics. However, in laparoscopic surgery, tactile feedback during grip is attenuated and limited to the resistance felt in the tool handle. Excessive grip force during laparoscopic surgery can lead to tissue damage. Providing additional supplementary tactile feedback may allow subjects to have better control of grip force and identification of tissue characteristics, potentially decreasing the learning curve associated with complex minimally invasive techniques.A tactile feedback system has been developed and integrated into a modified laparoscopic grasper that allows forces applied at the grasper tips to be felt by the surgeon's hands. In this study, 15 subjects (11 novices, 4 experts) were asked to perform single-handed peg transfers using these laparoscopic graspers in three trials (feedback OFF, ON, OFF). Peak and average grip forces (newtons) during each grip event were measured and compared using a Wilcoxon ranked test in which each subject served as his or her own control.After activating the tactile feedback system, the novice subject population showed significant decreases in grip force (p < 0.003). When the system was deactivated for the third trial, there were significant increases in grip force (p < 0.003). Expert subjects showed no significant improvements with the addition of tactile feedback (p > 0.05 in all cases).Supplementary tactile feedback helped novice subjects reduce grip force during the laparoscopic training task but did not offer improvements for the four expert subjects. This indicates that tactile feedback may be beneficial for laparoscopic training but has limited long-term use in the nonrobotic setting.
View details for DOI 10.1007/s00464-012-2612-x
View details for Web of Science ID 000316289200009
View details for PubMedID 23233002
- Design and Evaluation of Partial Weight-Bearing Sensor and Haptic Feedback System for Lower-Extremity Orthopedic Patients IEEE. 2013: 3378–83
Fabrication of a Thin-film Capacitive Force Sensor Array for Tactile Feedback in Robotic Surgery
IEEE. 2012: 2355–58
Although surgical robotic systems provide several advantages over conventional minimally invasive techniques, they are limited by a lack of tactile feedback. Recent research efforts have successfully integrated tactile feedback components onto surgical robotic systems, and have shown significant improvement to surgical control during in vitro experiments. The primary barrier to the adoption of tactile feedback in clinical use is the unavailability of suitable force sensing technologies. This paper describes the design and fabrication of a thin-film capacitive force sensor array that is intended for integration with tactile feedback systems. This capacitive force sensing technology could provide precise, high-sensitivity, real-time responses to both static and dynamic loads. Capacitive force sensors were designed to operate with optimal sensitivity and dynamic range in the range of forces typical in minimally invasive surgery (0-40 N). Initial results validate the fabrication of these capacitive force-sensing arrays. We report 16.3 pF and 146 pF for 1-mm(2) and 9-mm(2) capacitive areas, respectively, whose values are within 3% of theoretical predictions.
View details for Web of Science ID 000313296502144
View details for PubMedID 23366397
- In-vitro cell system for studying molecular mechanisms of action associated with low intensity focused ultrasound SPIE-INT SOC OPTICAL ENGINEERING. 2012
Applications of Tactile Feedback in Medicine
IOS PRESS. 2011: 703–9
A tactile feedback system has been developed in order to provide augmentative sensory feedback for a number of medical applications. The key component to the system is a pneumatic balloon-based tactile display, which can be scaled and adapted for a variety of configurations. The system also features pneumatic and electronic control system components, a commercial force sensor modified to fit the desired application. To date, this technology has been successfully applied to medical robotics, minimally invasive surgery, and rehabilitation medicine.
View details for DOI 10.3233/978-1-60750-706-2-703
View details for Web of Science ID 000392219500137
View details for PubMedID 21335884
Remote Tactile Sensing Glove-Based System
IEEE. 2010: 1550–54
A complete glove-based master-slave tactile feedback system was developed to provide users with a remote sense of touch. The system features a force-sensing master glove with piezoresistive force sensors mounted at each finger tip, and a pressure-transmitting slave glove with silicone-based pneumatically controlled balloon actuators, mounted at each finger tip on another hand. A control system translates forces detected on the master glove, either worn by a user or mounted on a robotic hand, to discrete pressure levels at the fingers of another user. System tests demonstrated that users could accurately identify the correct finger and detect three simultaneous finger stimuli with 99.3% and 90.2% accuracy, respectively, when the subjects were located in separate rooms. The glove-based tactile feedback system may have application to virtual reality, rehabilitation, remote surgery, medical simulation, robotic assembly, and military robotics.
View details for DOI 10.1109/IEMBS.2010.5626824
View details for Web of Science ID 000287964001236
View details for PubMedID 21096379
Characterization of a Pneumatic Balloon Actuator for Use in Refreshable Braille Displays
IOS PRESS. 2009: 94-+
Many existing refreshable Braille display technologies are costly or lack robust performance. A process has been developed to fabricate consistent and reliable pneumatic balloon actuators at low material cost, using a novel manufacturing process. This technique has been adapted for use in refreshable Braille displays that feature low power consumption, ease of manufacture and small form factor. A prototype refreshable cell, conforming to American Braille standards, was developed and tested. The cell was fabricated from molded PDMS to form balloon actuators with a spin-coated silicone film, and fast pneumatic driving elements and an electronic control system were developed to drive the Braille dots. Perceptual testing was performed to determine the feasibility of the approach using a single blind human subject. The subject was able to detect randomized Braille letters rapidly generated by the actuator with 100% character detection accuracy.
View details for DOI 10.3233/978-1-58603-964-6-94
View details for Web of Science ID 000272963000023
View details for PubMedID 19377122
A haptic feedback system for lower-limb prostheses
IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING
2008; 16 (3): 270–77
A haptic feedback system has been developed to provide sensory information to patients with lower-limb prostheses or peripheral neuropathy. Piezoresistive force sensors were mounted against four critical contact points of the foot to collect and relay force information to a system controller, which in turn drives four corresponding pneumatically controlled balloon actuators. The silicone-based balloon actuators were mounted on a cuff worn on the middle thigh, with skin contacts on the posterior, anterior, medial, and lateral surfaces of the thigh. Actuator characterization and human perceptual testing were performed to determine the effectiveness of the system in providing tactile stimuli. The actuators were determined to have a monotonic input pressure-vertical deflection response. Six normal subjects wearing the actuator cuff were able to differentiate inflation patterns, directional stimuli and discriminate between three force levels with 99.0%, 94.8%, and 94.4% accuracy, respectively. With force sensors attached to a shoe insole worn by an operator, subjects were able to correctly indicate the movements of the operator with 95.8% accuracy. These results suggest that the pneumatic haptic feedback system design is a viable method to provide sensory feedback for the lower limbs.
View details for DOI 10.1109/TNSRE.2008.920075
View details for Web of Science ID 000256966300007
View details for PubMedID 18586606
- Optimization of a Tactile Feedback System to Aid the Rehabilitation of Lower-Limb Amputees IEEE. 2008: 63
A Prototype Haptic Feedback System for Lower-Limb Prostheses and Sensory Neuropathy
IOS PRESS. 2008: 115-+
Lower-limb sensory loss as a result of peripheral neuropathy or amputation results in sub-optimal movement and an increased incidence of injury. While the adoption of lower-limb prostheses and therapeutic footwear can reduce tissue injury and support movement, the fundamental problem of sensory loss continues to exist. A prototype haptic feedback system has been developed to aid in the recovery of lower-limb sensation due to these causes. Thin-film force sensors placed at the critical points for gait and balance functions collect essential force data, which is delivered to the user via pneumatically controlled balloon inflation. It is postulated that the use of this system will increase the tactile awareness of a patient's lower-limb or prosthesis, and when used in concert with modern rehabilitation techniques will create a method that will reduce the duration and improve the quality of lower-limb rehabilitation, especially in gait and balance functions.
View details for Web of Science ID 000272668400025
View details for PubMedID 18391269