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As men age, the prostate continues to grow on average 2.5% per year. While the variable growth rate of the total prostate gland is recognized, the growth rate of different prostate zones remains largely unclear. We evaluated the growth patterns of the prostate zones and identified clinical parameters contributing to the zonal growth rates.Prostate magnetic resonance imaging (MRI) data and clinical information were obtained retrospectively on 156 patients who had at least 3 prostate MRIs between 2003 and 2018. Different prostate zonal volumes were measured and analyzed. The outcome was analyzed using linear regression.We observed that prostate growth rates vary depending on body mass index (BMI), transition zone index (TZI), the prostate zone and 5-alpha reductase inhibitor (5ARI) use. The peripheral zone volume growth rates increased with age and peaked at 60-70 years of age (p=0.047), while the transition zone volume demonstrates continuous growth without a peak through all ages. BMI and TZI are associated with the growth rate of the peripheral zone (p=0.026, p0.001, respectively) but not the transition zone growth rate. 5ARI use is significantly associated with the reduction in the transition zone growth rate (p=0.033), not the peripheral zone. In addition, patients with TZI greater than 60% had the most significant reduction in the transition zone growth rate while taking 5ARI (p0.001).Transition and peripheral zones of the prostate grow at variable rates. BMI and TZI affect peripheral zone growth rate, while 5ARI use reduces the transition zone growth rate.

Supplementary Data from Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer

Purpose:Pancreatic ductal adenocarcinoma (PDAC) remains a significant health issue. For most patients, there are no options for targeted therapy, and existing treatments are limited by toxicity. The HOPE trial (Harnessing Organoids for PErsonalized Therapy) was a pilot feasibility trial aiming to prospectively generate patient-derived organoids (PDO) from patients with PDAC and test their drug sensitivity and correlation with clinical outcomes.Experimental Design:PDOs were established from a heterogeneous population of patients with PDAC including both basal and classical PDAC subtypes.Results:A method for classifying PDOs as sensitive or resistant to chemotherapy regimens was developed to predict the clinical outcome of patients. Drug sensitivity testing on PDOs correlated with clinical responses to treatment in individual patients.Conclusions:These data support the investigation of PDOs to guide treatment in prospective interventional trials in PDAC.

Pancreatic cancer has the worst prognosis of all common tumors. Earlier cancer diagnosis could increase survival rates and better assessment of metastatic disease could improve patient care. As such, there is an urgent need to develop biomarkers to diagnose this deadly malignancy earlier. Analyzing circulating extracellular vesicles (cEVs) using ‘liquid biopsies’ offers an attractive approach to diagnose and monitor disease status. However, it is important to differentiate EV-associated proteins enriched in patients with pancreatic ductal adenocarcinoma (PDAC) from those with benign pancreatic diseases such as chronic pancreatitis and intraductal papillary mucinous neoplasm (IPMN). To meet this need, we combined the novel EVtrap method for highly efficient isolation of EVs from plasma and conducted proteomics analysis of samples from 124 individuals, including patients with PDAC, benign pancreatic diseases and controls. On average, 912 EV proteins were identified per 100µL of plasma. EVs containing high levels of PDCD6IP, SERPINA12 and RUVBL2 were associated with PDAC compared to the benign diseases in both discovery and validation cohorts. EVs with PSMB4, RUVBL2 and ANKAR were associated with metastasis, and those with CRP, RALB and CD55 correlated with poor clinical prognosis. Finally, we validated a 7-EV protein PDAC signature against a background of benign pancreatic diseases that yielded an 89% prediction accuracy for the diagnosis of PDAC. To our knowledge, our study represents the largest proteomics profiling of circulating EVs ever conducted in pancreatic cancer and provides a valuable open-source atlas to the scientific community with a comprehensive catalogue of novel cEVs that may assist in the development of biomarkers and improve the outcomes of patients with PDAC.

Purpose The purpose of the study is to determine if a combination of dermal thickening and subcutaneous fluid honeycombing on non-contrast MRI, termed the dermal rim sign (DRS), can be diagnostically analogous to dermal backflow seen on lymphoscintigraphy in patients with secondary upper extremity lymphedema. Materials and methods Upper extremity MRI and lymphoscintigraphy were performed on patients referred to a multidisciplinary lymphedema clinic for suspicion of secondary lymphedema. Sensitivity, specificity, and positive and negative predictive values of DRS on MRI in detecting dermal backflow on lymphoscintigraphy and the correlation between DRS, Indocyanine Green (ICG) lymphography, bioimpedence L-Dex® ratio and MRI Lymphedema Staging were calculated. Weighted interobserver agreements on the presence and location of DRS on MRI were calculated. Results Of the 45 patients in the study, 91.1% (41/45) of patients had history of breast cancer. The average age was 58.4 ± 10.5 years, with a mean symptom duration of 4.7 ± 4.4 years. The mean BMI was 30.5 ± 7.0 kg/m2. Interobserver agreement on the presence and the extent of DRS on MRI was 0.93 [95% confidence-interval: 0.80–1]. DRS was present in 97% (32/33) of patients who demonstrated dermal backflow on lymphoscintigraphy. Sensitivity, specificity, PPV, and NPV of DRS were 96.6% [81.7%–99.9%], and 75.0% [47.6%–92.7%], 87.5% [74.9%–94.3%], and 92.3% [63.1%–98.8%]. DRS was associated with severity on ICG lymphography and bioimpedance (both p Conclusions DRS on non-contrast MRI is highly predictive of dermal backflow and correlates with clinical measures of lymphedema severity. DRS may be used as an independent diagnostic biomarker to identify patients who would benefit from dedicated exams.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) remains a significant health issue. For most patients, there are no options for targeted therapy, and existing treatments are limited by toxicity. The HOPE trial (Harnessing Organoids for PErsonalized Therapy) was a pilot feasibility trial aiming to prospectively generate patient-derived organoids (PDO) from patients with PDAC and test their drug sensitivity and correlation with clinical outcomes. Experimental Design: PDOs were established from a heterogeneous population of patients with PDAC including both basal and classical PDAC subtypes. Results: A method for classifying PDOs as sensitive or resistant to chemotherapy regimens was developed to predict the clinical outcome of patients. Drug sensitivity testing on PDOs correlated with clinical responses to treatment in individual patients. Conclusions: These data support the investigation of PDOs to guide treatment in prospective interventional trials in PDAC.

To compare detection rates of NET liver metastases of MRI and Ga-68-DOTATATE PET/CT to provide more clarity when selecting diagnostic imaging tests for NET staging. In this IRB-approved single-institution retrospective study, all patients with pathology-proven NET who underwent Ga-68-DOTATATE and MRI scans within 8 weeks of each other (3/2017–2/2020) were reviewed. Number of metastases for each patient on diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) MRI, and Ga-68 DOTATATE were recorded by two blinded radiologists, followed by consensus review with two separate blinded readers for MRI and nuclear medicine. Per-lesion and -modality scoring at each lesion location were then performed in consensus. Per-patient linear regression was performed comparing MRI and Ga-68 DOTATATE detection rates for each reader and in consensus, and per-lesion-matched pair difference means were used to compare detection frequency between modalities. 32 patients (mean age 59 years, 59.4% male) and 90 liver metastases were analyzed. Intraclass coefficients (ICC) [95% CI] between the two readers were 0.97 [0.95, 0.99], 0.89 [0.82, 0.94], and 0.98 [0.97, 0.99] for Ga-68 DOTATATE, DWI, and DCE, respectively. Matched per-lesion mean differences were + 0.17 ± 0.07 (p = 0.01) and + 0.22 ± 0.06 (p =

Rationale and Objectives Radiology participation is necessary in oncology multidisciplinary conferences (MDCs), but the resources required to do so are often unaccounted for. In this prospective study we provide an analysis of resource utilization as a function of outcomes for all MDCs covered by an entire radiology section and provide a time-based cost estimate. Materials and Methods Following institutional review board approval, prospective data on all MDCs covered by abdominal radiologists at a single tertiary care academic center were obtained over nine weeks. A predefined questionnaire was used by a single observer who attended every imaging review and recorded the total time spent by the radiologists and several outcome measures. The total time recorded was used to provide a time-based cost estimate using a national salary survey. Results Six radiologists participated in a total of 57 MDCs, with 577 cases reviewed and discussed. 181 (31%) cases were performed at outside facilities requiring full reinterpretation. Clinically significant revisions to original reports were recorded in 107 (18.5%) cases. Radiologist input directly resulted in alteration of cancer staging in 65 (11%) patients and specific recommendations for follow-up diagnostic workup in 280 (48%) of cases. The mean total time devoted by the staff radiologist per week to MDCs was 18.7 hours/week, nearly a half of full-time effort, or 8% of total effort per radiologist. The total annual projected cost of radiology coverage for each weekly MDC was $26,920. Conclusion Section-wide radiologist participation in MDCs directly resulted in change in clinical management in nearly half of reviewed cases. This was achieved at a notable time cost, highlighting the need for efficient integration of radiology MDC participation into radiologist workflow and compensation models.

Lymphedema is a devastating disease that has no cure. Management of lymphedema has evolved rapidly over the past two decades with the advent of surgeries that can ameliorate symptoms. MRI has played an increasingly important role in the diagnosis and evaluation of lymphedema, as it provides high spatial resolution of the distribution and severity of soft tissue edema, characterizes diseased lymphatic channels, and assesses secondary effects such as fat hypertrophy. Many different MR techniques have been developed for the evaluation of lymphedema, and the modality can be tailored to suit the needs of a lymphatic clinic. In this review article we provide an overview of lymphedema, current management options, and the current role of MRI in lymphedema diagnosis and management. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 5.

Purpose Hepatic thermal ablation therapy can result in c-Met-mediated off-target stimulation of distal tumor growth. The purpose of this study was to determine if a similar effect on tumor metabolism could be detected in vivo with hyperpolarized 13C MRI. Materials and methods In this prospective study, female Fisher rats (n = 28, 120–150 g) were implanted with R3230 rat breast adenocarcinoma cells and assigned to either: sham surgery, hepatic radiofrequency ablation (RFA), or hepatic RFA + adjuvant c-Met inhibition with PHA-665752 (RFA + PHA). PHA-665752 was administered at 0.83 mg/kg at 24 h post-RFA. Tumor growth was measured daily. MRI was performed 24 h before and 72 h after treatment on 14 rats, and the conversion of 13C-pyruvate into 13C-lactate within each tumor was quantified as lactate:pyruvate ratio (LPR). Comparisons of tumor growth and LPR were performed using paired and unpaired t-tests. Results Hepatic RFA alone resulted in increased growth of the distant tumor compared to sham treatment (0.50 ± 0.13 mm/day versus 0.11 ± 0.07 mm/day; p Conclusion In vivo hyperpolarized 13C MRI can detect hepatic RFA-induced increase in lactate flux within a distant R3230 tumor, which correlates with increased tumor growth. Adjuvant inhibition of c-Met suppresses these off-target effects, supporting a role for the HGF/c-Met signaling axis in these tumorigenic responses.

HCC incidence continues to increase worldwide and is most frequently discovered at an advanced stage when limited curative options are available. Combination locoregional therapies have emerged to improve patient survival and quality of life or downstage patients to curative options. The increasing options for locoregional therapy combinations require an understanding of the expected post-treatment imaging appearance in order to assess treatment response. This review aims to describe the synergy between TACE combined with thermal ablation and TACE combined with SBRT. We will also illustrate expected imaging findings that determine treatment efficacy based on the mechanism of tissue injury using the LI-RADS Treatment Response Algorithm.

Multidisciplinary conferences (MDCs) play a major role in management and care of oncology patients. Hepatocellular carcinoma (HCC) is a complex disease benefiting from multidisciplinary discussions to determine optimal patient management. A multitude of liver-directed locoregional therapies have emerged allowing for more options for treatment of HCC. A radiologist dedicated to HCC-MDC is an important member of the team contributing to patient care in multiple ways. The radiologist plays a key role in image interpretation guiding initial therapy discussions as well as interpreting post-treatment imaging following liver-directed therapy. Standardization of image interpretation can lead to more consistent treatment received by the patient as well as accurate assessment of transplant eligibility. The radiologist can facilitate this process using structured reporting that is also supported by stakeholders involved in interdisciplinary management of liver diseases. The Liver Imaging Reporting and Data System (LI-RADS), is a living document which offers a standardized reporting algorithm for consistent communication of radiologic findings for HCC screening and characterization of liver observations in patients at risk for HCC. The LI-RADS post-treatment algorithm (LR-TR algorithm) has been developed to standardize liver observations following liver-directed locoregional therapy. This review article focuses on the role of the radiologist at HCC-MDC and implementation of the LR-TR algorithm for improving workflow.

Metabolic reprogramming, in particular, glycolytic regulation, supports abnormal survival and growth of hepatocellular carcinoma (HCC) and could serve as a therapeutic target. In this study, we sought to identify glycolytic regulators in HCC that could be inhibited to prevent tumor progression and could also be monitored in vivo, with the goal of providing a theragnostic alternative to existing therapies.An orthotopic HCC rat model was used. Tumors were stimulated into a high-proliferation state by use of off-target liver ablation and were compared with lower-proliferating controls. We measured in vivo metabolic alteration in tumors before and after stimulation, and between stimulated tumors and control tumors using hyperpolarizedGlycolytic lactate flux increased within HCC tumors 3 days after tumor stimulation, correlating positively with tumor proliferation as measured with Ki67. This was associated with a shift towards aerobic glycolysis and downregulation of the pentose phosphate pathway detected by mass spectrometry. MRI-measured lactate flux was most closely coupled with PFKFB3 expression and was suppressed with direct inhibition using PFK15.Inhibition of PFKFB3 prevents glycolytic-mediated HCC proliferation, trackable by in vivo h

OBJECTIVE To implement and evaluate outcomes from a comprehensive, multi-disciplinary debulking program in the United States. SUMMARY BACKGROUND DATA Interest in and access to surgical treatment for chronic lymphedema (LE) in the United States have increased in recent years, yet there remains little attention on liposuction, or debulking, as an effective treatment option. In some other countries, debulking is a common procedure for the surgical treatment of LE, is covered by insurance, and has demonstrated excellent, reproducible outcomes. In this study we describe our experience implementing a debulking technique from Sweden in the United States. METHODS Patients who presented with chronic lymphedema followed a systematic multi-disciplinary work-up. For debulking with power assisted liposuction, the surgical protocol was modeled after that developed by Hakan Brorson. A retrospective review of consecutive patients who underwent debulking at our institution was conducted. RESULTS Between December 2017 and January 2020, 39 patients underwent 41 debulking procedures with power assisted liposuction, including 23 upper and 18 lower extremities. Mean patient age was 58 years and 85% of patients had LE secondary to cancer, the majority of which (64%) was breast cancer. Patients experienced excess volume reductions of 111% and 115% in the upper and lower extremities, respectively, at one year post-operatively. Overall quality of life (LYMQOL) improved by a mean of 33%. Finally, patients reported a decreased incidence of cellulitis and decreased reliance on conservative therapy modalities post-operatively. CONCLUSIONS Debulking with power assisted liposuction is an effective treatment for patients with chronic extremity lymphedema. The operation addresses patient goals and improves quality of life, and additionally reduces extremity volumes, infection rates and reliance on outpatient therapy. A comprehensive, multi-disciplinary debulking program can be successfully implemented in the United States healthcare system.

Staging of upper extremity lymphedema is needed to guide surgical management, but is not standardized due to lack of accessible, quantitative, or precise measures. Here, we established an MRI-based staging system for lymphedema and validate it against existing clinical measures. Bilateral upper extremity MRI and lymphoscintigraphy were performed on 45 patients with unilateral secondary lymphedema, due to surgical intervention, who were referred to our multidisciplinary lymphedema clinic between March 2017 and October 2018. MRI short-tau inversion recovery (STIR) images were retrospectively reviewed. A grading system was established based on the cross-sectional circumferential extent of subcutaneous fluid infiltration at three locations, labeled MRI stage 0–3, and was compared to L-Dex®, ICG lymphography, volume, lymphedema quality of life (LYMQOL), International Society of Lymphology (ISL) stage, and lymphoscintigraphy. Linear weighted Cohen’s kappa was calculated to compare MRI staging by two readers. STIR images on MRI revealed a predictable pattern of fluid infiltration centered on the elbow and extending along the posterior aspect of the upper arm and the ulnar side of the forearm. Patients with higher MRI stage were more likely to be in ISL stage 2 (p = 0.002) or to demonstrate dermal backflow on lymphoscintigraphy (p = 0.0002). No correlation was found between MRI stages and LYMQOL. Higher MRI stage correlated with abnormal ICG lymphography pattern (rs = 0.63, p

Indocyanine green (ICG) lymphography is frequently used in the diagnosis of lymphedema, as well as the planning of its surgical management, but the typical anatomy of the superficial lymphatic pathways is incompletely delineated. This study aims to evaluate the topographical anatomy of superficial lymphatic vessels of the upper extremity METHODS: Sixty consecutive patients undergoing lymphaticovenular anastomosis for unilateral upper extremity lymphedema were selected. Lymphatic mapping was performed on the normal contralateral arm with ICG lymphography. A single upper arm reference line and two separate forearm reference lines (anterior and posterior) were drawn between anatomic landmarks. Lymphatic pathways were analyzed based on distances (cm) from the reference lines and were compared with those in lymphedema arms.Mean age of the patients were 54.6 ± 8.4 years. Three lymphatic flow pathways were identified: anterior (100%), posterior (96.6%), and posterior-ulnar lymphatic (33.3%) vessels. The anterior and posterior lymphatic vessels ran along the anterior and posterior reference lines, respectively, on the forearm (within 2 cm) and medial to the upper arm reference line. In arms with lymphedema, the absence of lymphatic flow was most commonly observed in posterior lymphatics (29/59, 49%), followed by anterior (15/60, 25%) and posterior-ulnar lymphatics (1/20, 5%). Compared to normal arms, new lymphatic flow through posterior-ulnar lymphatics was observed in 34.5% of patients (10/29) in whom posterior lymphatics was completely obstructed.Superficial lymphatic vessels can be classified into anterior, posterior, and posterior-ulnar lymphatic vessels. Posterior-ulnar lymphatic vessels might be least affected by lymphosclerosis in patients with lymphedema.

Mucin-producing neoplasms in the abdomen and pelvis are a distinct entity, separate from simple fluid-containing neoplasms and loculated fluid collections. Mucin is a thick gelatinous substance and-owing to its high water content-has imaging features that can be mistaken for those of simple fluid-containing neoplasms with multiple imaging modalities. However, mucin-producing neoplasms arise from specific organs in the abdomen and pelvis, with unique imaging appearances, knowledge of which is important to guide accurate diagnosis and management. With its large field of view and high soft-tissue resolution, MRI has advantages over other imaging modalities in characterizing these neoplasms. The authors focus on the spectrum of MRI features of such mucin-producing neoplasms and illustrate how-despite a varied organ origin-some of these neoplasms share similar MRI and histopathologic features, thereby helping narrow the differential diagnosis. One common finding in these tumors is that the presence of internal complexity and solid enhancing components increases as the degree of malignant transformation increases. Lack of internal complexity generally indicates benignity. These tumors have a varied range of prognosis; for example, a low-grade appendiceal mucinous neoplasm is indicative of a good prognosis, while a mucinous tumor of the rectum is known to manifest at an early age with aggressive behavior and poorer prognosis compared with its nonmucinous counterpart.

INTRODUCTION AND OBJECTIVE:MRI-targeted biopsy has emerged as a standard of care in the management of men with elevated PSA and prostate cancer on active surveillance. Although two main biopsy tech...

INTRODUCTION AND OBJECTIVE:Benign prostatic hyperplasia (BPH) is highly prevalent in elderly men and is a major cause of lower urinary tract symptoms (LUTS). The zonal growth rate of the prostate a...

BACKGROUND More than 100 million adults in the US suffer from prediabetes or type-2 diabetes. Noninvasive imaging of pancreas endocrine function might provide a surrogate marker of β-cell functional integrity loss linked to this disease. PURPOSE To noninvasively assess pancreatic blood-flow modulation following a glucose challenge using arterial spin labeling (ASL) MRI. STUDY TYPE Prospective. SUBJECTS Fourteen adults (30 ± 7 years old, 3M/11F, body mass index [BMI] = 24 ± 3 kg.m-2 ). FIELD STRENGTH/SEQUENCE 3T MRI / background-suppressed pseudocontinuous PCASL preparation with single-shot fast-spin-echo (FSE) readout before and after an oral glucose challenge using either fruit juice (n = 7) or over-the-counter glucose gel (n = 7). ASSESSMENT Subjects were fasting prior to initiation of oral stimulation, then dynamic perfusion measurements were performed every 2 minutes for 30 minutes. We quantified absolute blood flow at each timepoint. STATISTICAL TESTS Repeated-measures analysis of variance (ANOVA) followed by paired t-tests to assess for a significant effect of glucose challenge on measured perfusion. RESULTS Measured basal blood flow was 187 ± 53 mL/100g/min. A significant blood flow increase of +38 ± 26% was observed 10 minutes poststimulation (P < 0.05) and continuing until the end of the experiment. The gel stimulation provided the most consistent results, with an early rise followed by an additional later increase consistent with the known pancreatic insulin response to elevated blood glucose. Across-subject variations in blood flow increase were partially attributable to basal flow, with a negative correlation of r = -0.84 between basal and maximal relative flow increase in the gel group. DATA CONCLUSION ASL can be used to measure pancreatic flow in response to a glucose challenge, which could be linked to insulin release and secretion. This paradigm might be useful to characterize disorders of glucose regulation. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:854-860.

To determine sensitivity and specificity of the “duct-interrupted,” “corona,” and “attraction” signs on MR cholangio-pancreatography (MRCP) in distinguishing pancreatic head ductal adenocarcinoma (PDAC) from inflammatory pancreatic pseudomass (IPP). This study included 53 adults (33 men and 20 women, mean age, 55 years; range, 17–87 years) with a pancreatic head mass who underwent MRCP. Three blinded radiologists independently reviewed each MRCP exam and three signs were assessed: (1) the “duct-interrupted” sign, deemed positive for PDAC if the duct within the mass demonstrated complete interruption with upstream dilation; (2) the “corona” sign, considered positive for PDAC if dilated side-branches were located exclusively outside the mass; and (3) the “attraction” sign, deemed positive for IPP if the dilated common bile duct showed attraction and angulation towards the mass. Sensitivity, specificity, and positive and negative predictive values of the signs were calculated, as well as interobserver agreement. Out of 53 masses, 17 (32%) were PDAC and 36 (68%) were IPP. Sensitivity, specificity, and positive and negative predictive values of the “duct-interrupted” sign to differentiate between PDAC from IPP for the three readers were 29–53%, 89–95%, 56–82% and 73–81%, respectively (κ = 0.41); for the “corona” sign, they were 29–53%, 81–100%, 56–100%, and 75–78%, respectively (κ = 0.4), and for the “attraction” sign, they were 20–25%, 71–82%, 64–75%, and 31–34%, respectively (κ = 0.54). The “duct-interrupted” and “corona” MRCP signs have high specificity for diagnosing PDAC, while the “attraction” sign has good specificity for identifying IPP.

To compare detection rates of NET liver metastases of MRI and Ga-68-DOTATATE PET/CT to provide more clarity when selecting diagnostic imaging tests for NET staging.In this IRB-approved single-institution retrospective study, all patients with pathology-proven NET who underwent Ga-68-DOTATATE and MRI scans within 8 weeks of each other (3/2017-2/2020) were reviewed. Number of metastases for each patient on diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) MRI, and Ga-68 DOTATATE were recorded by two blinded radiologists, followed by consensus review with two separate blinded readers for MRI and nuclear medicine. Per-lesion and -modality scoring at each lesion location were then performed in consensus. Per-patient linear regression was performed comparing MRI and Ga-68 DOTATATE detection rates for each reader and in consensus, and per-lesion-matched pair difference means were used to compare detection frequency between modalities.32 patients (mean age 59 years, 59.4% male) and 90 liver metastases were analyzed. Intraclass coefficients (ICC) [95% CI] between the two readers were 0.97 [0.95, 0.99], 0.89 [0.82, 0.94], and 0.98 [0.97, 0.99] for Ga-68 DOTATATE, DWI, and DCE, respectively. Matched per-lesion mean differences were + 0.17 ± 0.07 (p = 0.01) and + 0.22 ± 0.06 (p = 0.001) for DWI versus Ga-68 DOTATATE and DCE vs Ga-68 DOTATATE, respectively, favoring MRI. Case-based linear regressions estimate that DWI and DCE detect 1.28 [1.07, 1.49] and 1.33 [1.12, 1.54] lesions, respectively, for each one detected on Ga-68 DOTATATE.MRI detects more hepatic NET metastasis in comparison to Ga-68 DOTATATE. Liver MRI should be performed in concert with Ga-68 DOTATATE in NET staging.

Rapid histologic assessment of fresh prostate biopsies may reduce patient anxiety, aid in biopsy sampling, and enable specimen triaging for molecular/genomic analyses and research that could benefit from fresh tissue analysis. Nonlinear microscopy (NLM) is a fluorescence microscopy technique that can produce high-resolution images of freshly excised tissue resembling formalin-fixed paraffin-embedded (FFPE) H&E. NLM enables evaluation of tissue up to ~100 µm below the surface, analogous to serial sectioning, but without requiring microtome sectioning. One hundred and seventy biopsies were collected from 63 patients who underwent in-bore MRI or MRI/ultrasound fusion biopsy procedures. Biopsies were stained in acridine orange and sulforhodamine 101, a nuclear and cytoplasmic/stromal fluorescent dye, for 45 s. Genitourinary pathologists evaluated the biopsies using NLM by translating the biopsies in real time to areas of interest and NLM images were recorded. After NLM evaluation, the biopsies were processed for standard FFPE H&E and similarities and differences between NLM and FFPE H&E were investigated. Accuracies of NLM diagnoses and Gleason scores were calculated using FFPE histology as the gold standard. Pathologists achieved a 92.4% sensitivity (85.0–96.9%, 95% confidence intervals) and 100.0% specificity (94.3–100.0%) for detecting carcinoma compared to FFPE histology. The agreement between the Grade Group determined by NLM versus FFPE histology had an unweighted Cohen’s Kappa of 0.588. The average NLM evaluation time was 2.10 min per biopsy (3.08 min for the first 20 patients, decreasing to 1.54 min in subsequent patients). Further studies with larger patient populations, larger number of pathologists, and multiple institutions are warranted. NLM is a promising method for future rapid evaluation of prostate needle core biopsies.

Multidisciplinary conferences (MDCs) play a major role in management and care of oncology patients. Hepatocellular carcinoma (HCC) is a complex disease benefiting from multidisciplinary discussions to determine optimal patient management. A multitude of liver-directed locoregional therapies have emerged allowing for more options for treatment of HCC. A radiologist dedicated to HCC-MDC is an important member of the team contributing to patient care in multiple ways. The radiologist plays a key role in image interpretation guiding initial therapy discussions as well as interpreting post-treatment imaging following liver-directed therapy. Standardization of image interpretation can lead to more consistent treatment received by the patient as well as accurate assessment of transplant eligibility. The radiologist can facilitate this process using structured reporting that is also supported by stakeholders involved in interdisciplinary management of liver diseases. The Liver Imaging Reporting and Data System (LI-RADS), is a living document which offers a standardized reporting algorithm for consistent communication of radiologic findings for HCC screening and characterization of liver observations in patients at risk for HCC. The LI-RADS post-treatment algorithm (LR-TR algorithm) has been developed to standardize liver observations following liver-directed locoregional therapy. This review article focuses on the role of the radiologist at HCC-MDC and implementation of the LR-TR algorithm for improving workflow.

PURPOSE: Hepatic thermal ablation therapy can result in c-Met-mediated off-target stimulation of distal tumor growth. The purpose of this study was to determine if a similar effect on tumor metabolism could be detected in vivo with hyperpolarized (13)C MRI. MATERIALS AND METHODS: In this prospective study, female Fisher rats (n=28, 120-150 g) were implanted with R3230 rat breast adenocarcinoma cells and assigned to either: sham surgery, hepatic radiofrequency ablation (RFA), or hepatic RFA + adjuvant c-Met inhibition with PHA-665752 (RFA+PHA). PHA-665752 was administered at 0.83 mg/kg at 24h post-RFA. Tumor growth was measured daily. MRI was performed 24h before and 72h after treatment on 14 rats, and the conversion of (13)C-pyruvate into (13)C-lactate within each tumor was quantified as lactate:pyruvate ratio (LPR). Comparisons of tumor growth and LPR were performed using paired and unpaired t tests. RESULTS: Hepatic RFA alone resulted in increased growth of the distant tumor compared to sham treatment (0.50±0.13 mm/day versus 0.11±0.07 mm/day; p

Background Tumor perfusion may inform therapeutic response and resistance in metastatic renal cell carcinoma (RCC) treated with antiangiogenic therapy. Purpose To determine if arterial spin labeled (ASL) MRI perfusion changes are associated with tumor response and disease progression in metastatic RCC treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Materials and Methods In this prospective study (ClinicalTrials.gov identifier: NCT00749320), metastatic RCC perfusion was measured with ASL MRI before and during sunitinib or pazopanib therapy between October 2008 and March 2014. Objective response rate (ORR) and progression-free survival (PFS) were calculated. Perfusion was compared between responders and nonresponders at baseline, at week 2, after cycle 2 (12 weeks), after cycle 4 (24 weeks), and at disease progression and compared with the ORR by using the Wilcoxon rank sum test and with PFS by using the log-rank test. Results Seventeen participants received sunitinib (mean age, 59 years ± 7.0 [standard deviation]; 11 men); 11 participants received pazopanib (mean age, 63 years ± 6.6; eight men). Responders had higher baseline tumor perfusion than nonresponders (mean, 404 mL/100 g/min ± 213 vs 199 mL/100 g/min ± 136; P = .02). Perfusion decreased from baseline to week 2 (-53 mL/100 g/min ± 31; P < .001), after cycle 2 (-65 mL/100 g/min ± 25; P < .001), and after cycle 4 (-79 mL/100 g/min ± 15; P = .008). Interval reduction in perfusion at those three time points was not associated with ORR (P = .63, .29, and .27, respectively) or PFS (P = .28, .27, and .32). Perfusion increased from cycle 4 to disease progression (51% ± 11; P < .001). Conclusion Arterial spin labeled perfusion MRI may assist in identifying responders to vascular endothelial growth factor receptor tyrosine kinase inhibitors and may help detect early evidence of disease progression in patients with metastatic renal cell carcinoma. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Goh and De Vita in this issue.

Purpose To assess the ability of the ring-enhancing sign and focal necrosis to diagnose adenosquamous carcinoma (ASqC), a variant of pancreatic ductal adenocarcinoma (PDAC), on MRI and CT. Methods The following features of ASqC and conventional PDAC were evaluated on CT and MRI: tumor size, location, margins, borders (non-exophytic, exophytic), and T1 signal intensity. Two readers, blinded to histopathology results, rated their confidence in detecting ring-enhancement and focal necrosis (FN) on a 5-point Likert scale on both MRI and CT. Inter-reader agreement was assessed with Cohen's kappa (k). Results A total of 24 patients were included: eight patients with treatment naive and histologically proven ASqC (six women, mean age: 63, range: 40–75) and 16 patients with PDAC (eight women, mean age: 67, range: 47–83). Statistically significant differences between ASqC and PDAC were seen in tumor size, location, presence of FN, and ring enhancement (p = 0.01–0.037). The readers were more confident in depicting the key differentiating feature ring-enhancement in ASqC on MRI compared to CT (confidence 1.71 ± 0.49 vs. 0.88 ± 0.35, p = 0.017) with moderate inter-reader agreement (k = 0.46 and 0.5, respectively). FN showed substantial inter-reader agreement on MR and moderate agreement on CT (k = 0.67 and 0.5, respectively). Conclusions Compared to CT, MRI depicts ring-enhancement in ASqC with greater reader confidence and FN in ASqC with higher inter-reader agreement. The concurrent presence of these two imaging features should raise high suspicion for ASqC.

To assess if a templated algorithm can improve the diagnostic performance of MRI for characterization of T2 isointense and hypointense renal masses.In this retrospective study, 60 renal masses with histopathologic diagnoses that were also confirmed as T2 iso- or hypointense on MRI were identified (mean ± standard deviation, range: 3.9 ± 2.5, 1.0-13.7 cm). Two semi-quantitative diagnostic algorithms were created based on MRI features of renal masses reported in the literature. Three body-MRI trained radiologists provided clinical diagnoses based on their experience and separately provided semiquantitative data for each components of the two algorithms. The algorithms were applied separately by a radiology trainee without additional interpretive input. Logistic regression was used to compare the accuracy of the three methods in distinguishing malignant versus benign lesions and in diagnosing the exact histopathology. Inter-reader agreement for each method was calculated using Fleiss' kappa statistics.The accuracy of the two algorithms and clinical experience were similar (70%, 69%, and 64%, respectively, p = 0.22-0.32), with fair to moderate inter-reader agreement (Fleiss's kappa: r = 0.375, r = 0.308, r = 0.375, respectively, all p 0.0001). The accuracy of the two algorithms and clinical experience in diagnosing specific histopathology were also no different from each other (34%, 29%, and 32%, respectively, p = 0.49-0.74), with fair to moderate inter-reader agreement (Fleiss's kappa: r = 0.20, r = 0.28, r = 0.375, respectively, all p 0.0001).Semi-quantitative templated algorithms based on MRI features of renal masses did not improve the ability to diagnose T2 iso- and hypointense renal masses when compared to unassisted interpretation by body MR trained subspecialists.

Quantifying lymph nodes in vascularized lymph node transfer (VLNT) has been performed using preoperative percutaneous ultrasound. The higher resolution and accuracy of intraoperative ultrasound (IOUS) over transcutaneous ultrasound has been demonstrated in the radiology literature for the identification and characterization of finer structures including hepatic lesions, pancreatic lesions, and biliary or pancreatic ducts. We hypothesize that IOUS during VLNT would be a superior method to quantify and map lymph nodes in our flaps. A prospectively collected database of patients undergoing VLNT over 3 years (October 2014 to October 2017) was reviewed. Patients who underwent IOUS during flap harvest, before pedicle ligation to simultaneously map and quantify the number of lymph nodes were included in the study. Twenty-one patients with an average age of 58.7 years and a mean BMI of 32.3 underwent VLNT with IOUS for chronic lymphedema during the study period. Extremity lymphedema was classified as Campisi IB (n = 7), IIA (n = 7), IIB (n = 5), and IIIA (n = 2). There were 14 superficial circumflex iliac artery flaps, including 4 performed concomitantly with a deep inferior epigastric perforator flap, 1 transverse cervical artery flap, and 6 omental flaps. The average number of lymph nodes transferred per IOUS was 4.3 for superficial circumflex iliac artery flaps, 4 for the transverse cervical artery flap, and 5.2 for the omental flaps. Intraoperative ultrasound allows the lymphatic surgeon to precisely map the location of lymph nodes which can guide intraoperative decision making. As there is no data correlating the number of lymph nodes transferred and outcomes after VLNT, developing a precise intraoperative quantification method is important.

Aim: Although vascularized lymph node transplantation (VLNT) has gained recognition as an effective treatment option for lymphedema, no consensus on the timing of transplant with other lymphatic procedures has been established. The aim of this study is to describe our institutional experience with VLNT, including our staged approach and report postoperative outcomes. Methods: A retrospective review of patients who underwent VLNT for upper extremity lymphedema from May 2017 to April 2022 was conducted. Patients were divided into fat- or fluid-dominant phenotypes based on preoperative workup. Patients with a minimum of 12-month follow-up were included. Records were reviewed for demographic, intraoperative, and surveillance data. Results: Twenty-three patients underwent VLNT of the upper extremity during the study period, of which eighteen met the study criteria. Nine patients had fluid-dominant disease and nine patients had fat-dominant disease and had undergone prior debulking at our institution. Fluid-dominant patients demonstrated slight reductions in limb volume and hours in compression, and improvement in quality-of-life scores at twelve months. Fat-dominant patients who underwent prior debulking had a slight increase in limb volume without a change in hours of compression, and demonstrated improvements in quality-of-life scores in nearly all subdomains. Overall, 17% of patients discontinued compression therapy entirely. Improvement in extremity edema was present in 83% of postoperative MRIs. Conclusion: VLNT had varying effects on limb measurements while reliably improving quality-of-life and allowing for the potential of discontinuing compression. Utilizing a staged approach wherein debulking is performed upfront may be particularly beneficial for patients with fat-dominant disease.

Staging of upper extremity lymphedema is needed to guide surgical management, but is not standardized due to lack of accessible, quantitative, or precise measures. Here, we established an MRI-based staging system for lymphedema and validate it against existing clinical measures.Bilateral upper extremity MRI and lymphoscintigraphy were performed on 45 patients with unilateral secondary lymphedema, due to surgical intervention, who were referred to our multidisciplinary lymphedema clinic between March 2017 and October 2018. MRI short-tau inversion recovery (STIR) images were retrospectively reviewed. A grading system was established based on the cross-sectional circumferential extent of subcutaneous fluid infiltration at three locations, labeled MRI stage 0-3, and was compared to L-Dex®, ICG lymphography, volume, lymphedema quality of life (LYMQOL), International Society of Lymphology (ISL) stage, and lymphoscintigraphy. Linear weighted Cohen's kappa was calculated to compare MRI staging by two readers.STIR images on MRI revealed a predictable pattern of fluid infiltration centered on the elbow and extending along the posterior aspect of the upper arm and the ulnar side of the forearm. Patients with higher MRI stage were more likely to be in ISL stage 2 (p = 0.002) or to demonstrate dermal backflow on lymphoscintigraphy (p = 0.0002). No correlation was found between MRI stages and LYMQOL. Higher MRI stage correlated with abnormal ICG lymphography pattern (rAn MRI staging system for upper extremity lymphedema offers an improved non-invasive precision marker for lymphedema for therapeutic planning.• Diagnosis and staging of patients with secondary upper extremity lymphedema may be performed with non-contrast MRI, which is non-invasive and more readily accessible compared to lymphoscintigraphy and evaluation by lymphedema specialists. • MRI-based staging of secondary upper extremity lymphedema is highly reproducible and could be used for long-term follow-up of patients. • In patients with borderline clinical measurements, MRI can be used to identify patients with early-stage lymphedema.

Hepatocellular carcinoma (HCC) is the 4th leading cause of cancer-related death worldwide. Despite therapeutic advancements, a significant proportion of patients progress, highlighting the need to improve diagnostic approaches to monitor therapy. Radiofrequency ablation (RFA), an accepted locoregional therapy for early HCC, can stimulate more aggressive tumor biology within under-treated or distant tumors. Increased glycolytic activity is a hallmark feature of cancer, but variations in metabolism and its link to tumor aggression can impact the sensitivity of HCC to therapies affecting these pathways. Tumor metabolic phenotypes can be characterized by hyperpolarized 13C MRI (h13C MRI), which can also be used to assess treatment response. In this study, we used orthotopic rat HCC models with two different cell lines N1S1 and MCA-RH7777, and analyzed their mRNA expression of glycolysis-related genes and in vivo glycolytic activity with h13C MRI. We then partially-treated tumors with radiofrequency ablation (RFA) and used h13C MRI to measure in vivo tumor metabolism before and 3 days after RFA to compare them to histologic and phenotypical measures of disease progression. N1S1 tumors grew only as single lesions, while MCA-RH7777 rapidly produced intra-hepatic and distal metastases. Glycolysis-related genes including HK2, HK3, PFKFB3, and MCT4 were highly expressed in N1S1, but not in MCA-RH7777, while GPT1 was highly expressed in MCA-RH7777 but not in N1S1. In vivo h13C MRI demonstrated significantly increased 13C lactate flux in N1S1 tumor compared to the background normal liver, while 13C lactate flux in MCA-RH7777 rat model did not, consistent with mRNA expression patterns. Tumor 13C lactate flux was significantly increased and 13C alanine flux was significantly decreased following partial RFA treatment to N1S1 tumors when compared to untreated tumors, which was associated with an increase in tumor Ki67 expression. However, no change was seen on h13C MRI between the RFA and control arms in MCA-RH7777 tumors, even though growth and total tumor burden progressed significantly more following RFA. In contrast to N1S1, there was also no difference between 13C lactate flux and 13C alanine flux within MCA-RH7777 tumors and the neighboring normal hepatic parenchyma, suggesting that glycolytic activity in these tumors did not drive RFA-stimulated progression. Targeting of glycolytic pathways as a potential therapy for HCC may therefore be limited to certain subtypes, and h13C MRI may be used to select for sensitivity. Citation Format: Qianhui Dou, Aaron K. Grant, Cody Callahan, Muneeb Ahmed, Leo L. Tsai. Variations in glycolytic activity of HCC subtypes as monitored by in vivo h 13C MRI [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2807.

The HOPE trial (Harnessing Organoids for PErsonalized Therapy) was a pilot study to test the feasibility of generating patient derived organoids (PDOs) from patients with pancreatic cancer under real world conditions, test drug sensitivity against these PDOs, and correlate these findings with clinical outcomes. Biopsies were obtained primarily during routine clinical care from surgical specimens, ascites, fine needle biopsies (FNB) of primary tumors, and IR guided core biopsies of liver and lymph node metastases. PDOs were grown in WNT free media according to our previously published methods. PDO drug sensitivity testing was performed on a panel of drugs, AUC calculated, and sensitivity ranked. Patients were followed clinically and assessed for disease control. At data cutoff (January 2020), we enrolled a total of 76 subjects representing all stages of disease. Drug testing was performed successfully on PDOs generated from 12 of these subjects (16%). Factors contributing to success obtaining sufficient cells for PDO generation included modality, body part, and tumor cellularity. H&E and IHC corresponded in matched PDOs and donor tumors, as did DNA alterations. Transcriptomes of PDOs were classified as both ‘basal' and ‘classical' subtypes. When AUC values were annotated with clinical data, the Jenks break of 1.69 segregated matched PDO/AUC values into disease control and progressive disease. We estimated that a PDO AUC value 99% probability of disease control from a regimen that contains this drug, whereas if all drugs in a regimen had an AUC > 2.75 there is a > 80% probability of accurately predicting resistance. To illustrate the potential of PDO testing to tailor treatment for an individual patient, we described a case of a subject with stage IV PDAC with a KRAS mutation and ERBB2 amplification. The subject had disease control with FOLFIRINOX, which was held for toxicity. The PDO showed resistance to oxaliplatin and the patient subsequently had an extended period of disease control with regimens which did not include oxaliplatin, highlighting the potential of PDO drug sensitivity testing to exclude ineffective treatments from combination chemotherapy and limit toxicity. In conclusion, we have shown the feasibility of collecting material via real-world clinical practice sufficient to develop PDOs suitable for rapidly screening multiple drugs, and have shown a high degree of correlation between clinical outcomes in patients with PDAC and matched PDO drug sensitivity. We determined preliminary criteria based on the AUC of individual drugs in PDOs to predict drug sensitivity in subjects. These results highlight the potential of PDOs to personalize therapy and allow for the exclusion of ineffective drugs from combination regimens thereby reducing toxicity. We anticipate this approach will be used in future trials to prospectively inform treatment selection for patients with PDAC. Citation Format: Joseph Elan Grossman, Ling Huang, Lakshmi Muthuswamy, Sofia Perea, Dipikaa Akshinthala, Raul Gonzalez, Leo Tsai, Jonah Cohen, Mandeep Sawhney, Douglas Pleskow, Tyler M. Berzin, Bruno Bockorny, Andrea Bullock, Benjamin Schlechter, Mary Linton B. Peters, Catherine Conahan, Supraja Narasimhan, Christine Lim, Roger Davis, Robert Besaw, Martin Smith, Tara Kent, Mark Callery, Senthil K. Muthuswamy, Manuel Hidalgo. Organoid sensitivity in pancreatic cancer correlates with clinical response to treatment and reveals utility for reducing toxicity: Preliminary results from the HOPE trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT119.

Thermal ablation (TA) is an accepted therapy for early HCC and hepatic metastases from colorectal and breast cancers. However, suboptimal TA is a risk factor for early HCC recurrence and has been associated with a reduction in overall survival. This effect has been attributed to hypoxic response in periablative tissue mediated by HIF-1. Malignant transformation leads to increased anaerobic glycolysis even under normoxic conditions. This process is detectable by hyperpolarized 13C MRI (h13C MRI), which enables real-time high-resolution imaging of the conversion from pyruvate to lactate and may be used as a potential predictor for therapeutic response in HCC. We have identified two potential metabolic regulators and therapeutic targets with a direct link to lactate flux which may be monitored with h13C MRI. PFKFB3 has been identified as a crucial metabolic factor in several cancer types, encoding for inducible 6-phosphofructo-2-kinase and enhancing production of F2,6P2, consequently activating PK1 and glycolysis. Expression levels of PFKFB3 have been found to be higher in malignancies than in normal tissues, attributed to loss of glycolytic control and accelerating neoplastic activity. Hexokinase 3 (HK3), a key catalyst in the first committed steps in glucose metabolism, is also a key promoter involved in epithelial-mesenchymal transition. When we exposed an HCC rat cell line, N1S1, to heat stress, simulating the marginal zone of TA therapy, 20%-90% of cells survived at 40°C-50°C and there was no survival by 55°C. 5-8 days following this treatment, cell proliferation and mRNA expression of glycolysis-related genes were analyzed. Cellular proliferation rate was significantly higher in the heat-treated groups. mRNA expression of PFKFB3 was increased after thermal treatment, while HK3 expression was significantly decreased. We then developed an in vivo orthotopic rat model of a solitary N1S1 HCC and used h13C MRI to measure in vivo tumor lactate flux in response to radiofrequency ablation (RFA), a type of thermal ablation, of adjacent normal hepatic tissue, simulating local treatment of a distant lesion. h13C MRI demonstrated significantly increased tumor 13C lactate flux in the RFA arm relative to the control group (change in lactate-to-pyruvate ratio of 0.236±0.278 vs -0.035±0.107, p=0.0465, n=6), while background liver lactate flux was unchanged. We found that this correlated with mRNA expression of PFKFB3 and HK3, which was statistically significantly greater within tumors from the RFA group compared to control tumors (PFKFB3, 1.052±0.091 vs 0.655±0.294, p=0.0004, n=6; HK3, 0.751±0.130 vs 0.501±0.163, p=0.0036, n=6). The PFKFB3 expression patterns were concordant between in vitro and in vivo experiments. Our data shows that PFKFB3 may be an attractive treatment target for HCC, and h13C MRI may be a noninvasive technique well-suited to monitor treatment response. Citation Format: Qianhui Dou, Aaron K. Grant, Cody Callahan, David Mwin, Muneeb Ahmed, Leo L. Tsai. 13C-MRI detects increased lactate flux in HCC following hepatic thermal A\ablation and correlates with PFKFB3 Expression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2785.