Psychological Burden of Systemic Racism-Related Distress in New York City Healthcare Workers During the COVID-19 Pandemic.

BACKGROUND: Little is known about the relationship among systemic racism, psychological symptoms (depression, anxiety, and/or post-traumatic stress disorders), and burnout in healthcare workers (HCWs). OBJECTIVE: To determine whether distress related to awareness of systemic racism contributes to psychological symptoms and/or burnout in HCWs. We explored whether this form of racism-related distress may moderate the relationship between race, ethnicity, psychological symptoms, and burnout. DESIGN: A cross-sectional survey was conducted from November 19, 2020, through January 11, 2021. Statistical analysis was conducted from May 3, 2022, to June 15, 2022. PARTICIPANTS: Frontline HCWs at an urban tertiary care hospital in New York City. MAIN MEASURES: Distress related to awareness of systemic racism (SR) and racial disparities in COVID-19 outcomes (RD), psychological symptoms, and burnout. KEY RESULTS: Two thousand one of 4654 HCWs completed the survey (response rate 43.0%). Most HCWs reported experiencing distress related to awareness of systemic racism (1329 [66.4%]) and to racial disparities in COVID-19 outcomes (1137 [56.8%]). Non-Hispanic Black participants (SR odds ratio (OR) 2.84, p < .001; RD OR 2.34, p < .001), women (SR OR 1.35, p = .01; RD OR 1.67, p < .001), and those with history of mental illness (SR OR 2.13, p < .001; RD OR 1.66, p < .001) were more likely to report SR- and RD-related distress, respectively. HCWs who experienced "quite-a-bit to extreme" SR-related distress were more likely to screen positive for psychological symptoms (OR 5.90, p < .001) and burnout (OR 2.26, p < .001). CONCLUSIONS: Our findings suggest that distress related to awareness of systemic racism, not race/ethnicity, was associated with experiencing psychological symptoms and burnout in HCWs. As the medical community continues to critically examine the role of systemic racism in healthcare, our work is a first step in characterizing its toll on the psychological well-being of HCWs.

Designer membraneless organelles sequester native factors for control of cell behavior.

Subcellular compartmentalization of macromolecules increases flux and prevents inhibitory interactions to control biochemical reactions. Inspired by this functionality, we sought to build designer compartments that function as hubs to regulate the flow of information through cellular control systems. We report a synthetic membraneless organelle platform to control endogenous cellular activities through sequestration and insulation of native proteins. We engineer and express a disordered protein scaffold to assemble micron-size condensates and recruit endogenous clients via genomic tagging with high-affinity dimerization motifs. By relocalizing up to 90% of targeted enzymes to synthetic condensates, we efficiently control cellular behaviors, including proliferation, division and cytoskeletal organization. Further, we demonstrate multiple strategies for controlled cargo release from condensates to switch cells between functional states. These synthetic organelles offer a powerful and generalizable approach to modularly control cell decision-making in a variety of model systems with broad applications for cellular engineering.

Leveraging Clerkship Experiences to Address Segregated Care: A Survey-Based Approach to Student-Led Advocacy.

Phenomenon: Many academic medical centers (AMCs) have a history of separating patients on the basis of insurance status. In New York State, where Black and Latino patients are more than twice as likely to have Medicaid as white patients, this practice leads to de facto racial segregation in healthcare. Emerging evidence suggests that this segregation of care is detrimental to both patient care and medical education. Medical students are uniquely positioned to be change makers in this space but face significant barriers to speaking out about these disparities and successfully advocating for institutional change. Approach: The authors designed, piloted, and distributed a 16-item survey on segregated care to third-year medical students at a large academic medical center in New York City. Students were asked both open- and close-ended questions about witnessing separation and differences in patient care on the basis of insurance during their clinical rotations. The survey was shared with 140 students in March 2019 with a response rate of 46.4% (n = 65). Preliminary findings were presented to school and hospital administrators. Findings: More than half of survey respondents reported witnessing separation of patient care or differences in patient care on the basis of insurance (56.3%, n = 36 and 51.6%, n = 33 respectively). Many students reported that these experiences contributed to cynicism and burnout. The authors leveraged these results to advocate for quality improvement measures. In Ob-Gyn, department leadership launched a clinical transformation taskforce and recruited a new Vice Chair of Clinical Transformation/Chief Patient Experience Officer, whose role includes addressing segregated care and disparities in health outcomes. The hospital committed to establishing integrated practices in new clinical spaces and launching a similar survey among house staff. Insights: Many medical students experience and participate in segregated care during their clerkships and this has the potential to impact their education. Medical students are well-positioned to recognize segregated care across health systems and leverage their experiences for advocacy. A survey-based approach can be a powerful tool enabling students to collect these experiences to address segregated care and other health equity issues.

Protein Condensate Formation via Controlled Multimerization of Intrinsically Disordered Sequences.

Many proteins harboring low complexity or intrinsically disordered sequences (IDRs) are capable of undergoing liquid-liquid phase separation to form mesoscale condensates that function as biochemical niches with the ability to concentrate or sequester macromolecules and regulate cellular activity. Engineered disordered proteins have been used to generate programmable synthetic membraneless organelles in cells. Phase separation is governed by the strength of interactions among polypeptides with multivalency enhancing phase separation at lower concentrations. Previously, we and others demonstrated enzymatic control of IDR valency from multivalent precursors to dissolve condensed phases. Here, we develop noncovalent strategies to multimerize an individual IDR, the RGG domain of LAF-1, using protein interaction domains to regulate condensate formation in vitro and in living cells. First, we characterize modular dimerization of RGG domains at either terminus using cognate high-affinity coiled-coil pairs to form stable condensates in vitro. Second, we demonstrate temporal control over phase separation of RGG domains fused to FRB and FKBP in the presence of dimerizer. Further, using a photocaged dimerizer, we achieve optically induced condensation both in cell-sized emulsions and within live cells. Collectively, these modular tools allow multiple strategies to promote phase separation of a common core IDR for tunable control of condensate assembly.

Rheumatology Clinic Staff Needs: Barriers and Strategies to Addressing High Blood Pressure and Smoking Risk.

OBJECTIVE: Patients with rheumatologic conditions are at elevated risk of cardiovascular disease (CVD) due to inflammatory and traditional risk factors, such as high blood pressure (BP) and smoking. However, rheumatology clinics rarely address traditional risk factors, although they are routinely assessed and modifiable in primary care. The present study sought to (1) characterize rheumatology clinic staff's work process for addressing high BP and smoking and (2) identify barriers and strategies for effective management of these risk factors. METHODS: We conducted 7 focus groups with medical assistants, nurses, and scheduling staff from 4 adult rheumatology clinics across 2 health systems (BP focus groups, n = 23; smoking, n = 20). Transcripts were analyzed using thematic analysis to elucidate barriers and strategies. RESULTS: We found 3 clinic work processes for the management of high BP and smoking risk: (1) risk identification, (2) follow-up within the clinic, and (3) follow-up with primary care and community resources. Within these processes, we identified barriers and strategies grouped into themes: (1) time, (2) clinic workflows, (3) technology and resources, (4) staff's attitudes and knowledge, and (5) staff's perceptions of patients. The most pervasive barriers were (1) no structured system for follow-up and (2) staff confidence and skill in initiating conversations about health-related behavior change. CONCLUSIONS: Our study identified generalizable gaps in rheumatology staff's work processes and competencies for addressing high BP and smoking in patients. Future efforts to support staff needs should target (1) systems for follow-up within and outside the clinic and (2) conversation support tools.

First year medical student perceptions of physician advocacy and advocacy as a core competency: A qualitative analysis.

PURPOSE: Medical societies have embraced advocacy as a core professional competency, but little is known about how entering medical students view physician advocacy. This study examined how first year medical students define advocacy, their motivations for and anticipated challenges to advocacy, and whether they believe advocacy should be a core competency. METHOD: This study used a qualitative content analysis approach to analyze first year medical student narrative responses about physician advocacy. The analysis included the written responses of 95% of the first-year medical students at the University of California, San Francisco (UCSF) School of Medicine during two academic years. RESULTS: Students shared consensus that physicians should advocate on behalf of their individual patients. Students had varying opinions on whether all physicians should engage in societal level advocacy and whether it should be a core competency in medical school. Students find several compelling reasons for physicians to engage in societal advocacy but nevertheless anticipate challenges to physician advocacy. CONCLUSION: Given increasing consensus that advocacy is a core competency of physicians, providing medical students the skills to successfully engage in advocacy is increasingly important. Any new mandatory curricula will need to focus on how to engage learners with varied views on advocacy.

Assessment to Optimize Learning Strategies: A Qualitative Study of Student and Faculty Perceptions.

Phenomenon: The format of medical knowledge assessment can promote students' use of effective learning strategies from the learning sciences literature, such as elaboration, interleaving, retrieval practice, and distributed learning. Assessment format can also influence faculty teaching. Accordingly, our institution implemented a new assessment strategy in which pre-clerkship medical students answered weekly formative quizzes with constructed response questions (also referred to as open-ended questions) and multiple-choice questions in preparation for summative open-ended question examinations, to support students' use of recommended learning strategies. Our qualitative study explored medical student and faculty perceptions of this assessment strategy on learning and teaching. Approach: We conducted semi-structured interviews with 16 second-year medical students to explore their preparation for quizzes and summative examinations. We also interviewed 10 faculty responsible for writing and grading these assessments in the pre-clerkship foundational sciences curriculum regarding their approach to writing assessments and rubrics, and their perceptions of how their teaching may have changed with this assessment strategy. We analyzed interview transcripts using thematic analysis with a priori sensitizing concepts from the learning sciences literature. Findings: We identified four major themes characterizing student and faculty perceptions of weekly formative quizzes and summative OEQ examinations. Participants found that this assessment strategy helped (1) prioritize conceptual understanding, (2) simulate clinical problem solving, and (3) engage students and faculty in continuous improvement in their approach to learning or teaching. Faculty and students also recognized challenges and potential tradeoffs associated with these assessment formats. Participants identified (4) facilitators and barriers when implementing this assessment strategy. Insights: Our findings suggested that assessment of medical knowledge through weekly formative quizzes and summative open-ended question examinations can facilitate students' use of effective learning strategies. Faculty also recognized improvements in their teaching and in quality of assessment. This format of assessment also presented some challenges and potential tradeoffs and significant institutional resources were required for implementation.

Analysis of Gastrointestinal and Hepatic Manifestations of SARS-CoV-2 Infection in 892 Patients in Queens, NY.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus responsible for coronavirus disease 2019 (COVID-19).1,2 The virus enters cells via the angiotensin-converting enzyme 2 receptor, which is present in enterocytes in the ileum and colon.3 Gastrointestinal (GI) manifestations include diarrhea, nausea, vomiting, and abdominal pain, and the prevalence of GI symptoms varies greatly, with a range between 2% and 57%.4 In addition, abnormal liver chemistries are reported commonly.4 As a medical center at the forefront of the early epidemic in the United States, we seek to contribute to the growing body of literature that outlines the gastrointestinal and hepatic manifestations of COVID-19.

Kinase activity in the olfactory bulb is required for odor memory consolidation.

Long-term fear memory formation in the hippocampus and neocortex depends upon brain-derived neurotrophic factor (BDNF) signaling after acquisition. Incremental, appetitive odor discrimination learning is thought to depend substantially on the differentiation of adult-born neurons within the olfactory bulb (OB)-a process that is closely associated with BDNF signaling. We sought to elucidate the role of neurotrophin signaling within the OB on odor memory consolidation. Male mice were trained on odor-reward associative discriminations after bilateral infusion of the kinase inhibitor K252a, or vehicle control, into the OB. K252a is a partially selective inhibitor of tyrosine kinase (Trk) receptors, including the TrkB receptor for BDNF, though it also inhibits other plasticity-related kinases such as PKC and CaMKII/IV. K252a infusion into the OB did not impair odor acquisition or short-term (2 h) memory for the learned discriminations, but significantly impaired long-term (48 h) odor memory (LTM). This LTM deficit also was associated with reduced selectivity for the conditioned odorant in a reward-seeking digging task. Infusions of K252a immediately prior to testing did not impair LTM recall. These results indicate that kinase activation in the OB is required for the consolidation of odor memory of incrementally acquired information.

Side-to-side elbow range of movement variability in an ulnar neurodynamic test sequence variant in asymptomatic people.

BACKGROUND: Range of motion (ROM) asymmetry between sides is one indicator of a positive neurodynamic test, but this has been less well studied for the ulnar nerve. OBJECTIVE: The purpose of this study was to investigate side-to-side variation in elbow ROM during an ulnar neurodynamic test sequence, including contralateral cervical side flexion, in 40 asymptomatic subjects. METHODS: A traditional goniometer was used to measure elbow flexion ROM at two end points, onset of resistance ( R 1) and symptom onset ( P 1). Two repeated measures of R 1 and P 1 were taken on each side. RESULTS: Reliability for R 1 and P 1 was found to be good (ICC ≥ 0 . 83 , SEM ≤ 5 . 37 ) with no significant difference in mean ROM between sides. A significant relationship between sides was seen ( r values ≥ 0 . 48 ) and R 2 values > 0 . 23 ; this indicates at least 23% of the variance observed in one limb was accounted for by range in the opposite limb. This relationship was slightly stronger for R 1 than P 1. Lower bound scores indicate that intra-individual ROM difference > 2 3 ° for R 1 and 22° for P 1 would exceed normal ROM asymmetry. CONCLUSION: These findings provide clinicians with background information of ROM asymmetry during the ulnar neurodynamic test.

Artificial intelligence in musculoskeletal applications: a primer for radiologists.

As an umbrella term, artificial intelligence (AI) covers machine learning and deep learning. This review aimed to elaborate on these terms to act as a primer for radiologists to learn more about the algorithms commonly used in musculoskeletal radiology. It also aimed to familiarize them with the common practices and issues in the use of AI in this domain.

Longitudinal registration of T1-weighted breast MRI: A registration algorithm (FLIRE) and clinical application.

PURPOSE: MRI is commonly used to aid breast cancer diagnosis and treatment evaluation. For patients with breast cancer, neoadjuvant chemotherapy aims to reduce the tumor size and extent of surgery necessary. The current clinical standard to measure breast tumor response on MRI uses the longest tumor diameter. Radiologists also account for other tissue properties including tumor contrast or pharmacokinetics in their assessment. Accurate longitudinal image registration of breast tissue is critical to properly compare response to treatment at different timepoints. METHODS: In this study, a deformable Fast Longitudinal Image Registration (FLIRE) algorithm was optimized for breast tissue. FLIRE was then compared to the publicly available software packages with high accuracy (DRAMMS) and fast runtime (Elastix). Patients included in the study received longitudinal T1-weighted MRI without fat saturation at two to six timepoints as part of asymptomatic screening (n = 27) or throughout neoadjuvant chemotherapy treatment (n = 32). T1-weighted images were registered to the first timepoint with each algorithm. RESULTS: Alignment and runtime performance were compared using two-way repeated measure ANOVAs (P < 0.05). Across all patients, Pearson's correlation coefficient across the entire image volume was slightly higher with statistical significance and had less variance for FLIRE (0.98 ± 0.01 stdev) compared to DRAMMS (0.97 ± 0.03 stdev) and Elastix (0.95 ± 0.03 stdev). Additionally, FLIRE runtime (10.0 mins) was 9.0 times faster than DRAMMS (89.6 mins) and 1.5 times faster than Elastix (14.5 mins) on a Linux workstation. CONCLUSION: FLIRE demonstrates promise for time-sensitive clinical applications due to its accuracy, robustness across patients and timepoints, and speed.

Harnessing big data for health equity through a comprehensive public database and data collection framework.

The United States Department of Health and Human Services (HHS) pledged $90 million to help reduce health disparities with data-driven solutions. The funds are being distributed to 1400 community health centers, serving over 30 million Americans. Given these developments, our piece examines the reasons behind the delayed adoption of big data for healthcare equity, recent efforts embracing big data tools, and methods to maximize potential without overburdening physicians. We additionally propose a public database for anonymized patient data, introducing diverse metrics and equitable data collection strategies, providing valuable insights for policymakers and health systems to better serve communities.

Synthetic Knee MRI T1p Maps as an Avenue for Clinical Translation of Quantitative Osteoarthritis Biomarkers.

A 2D U-Net was trained to generate synthetic T1p maps from T2 maps for knee MRI to explore the feasibility of domain adaptation for enriching existing datasets and enabling rapid, reliable image reconstruction. The network was developed using 509 healthy contralateral and injured ipsilateral knee images from patients with ACL injuries and reconstruction surgeries acquired across three institutions. Network generalizability was evaluated on 343 knees acquired in a clinical setting and 46 knees from simultaneous bilateral acquisition in a research setting. The deep neural network synthesized high-fidelity reconstructions of T1p maps, preserving textures and local T1p elevation patterns in cartilage with a normalized mean square error of 2.4% and Pearson's correlation coefficient of 0.93. Analysis of reconstructed T1p maps within cartilage compartments revealed minimal bias (-0.10 ms), tight limits of agreement, and quantification error (5.7%) below the threshold for clinically significant change (6.42%) associated with osteoarthritis. In an out-of-distribution external test set, synthetic maps preserved T1p textures, but exhibited increased bias and wider limits of agreement. This study demonstrates the capability of image synthesis to reduce acquisition time, derive meaningful information from existing datasets, and suggest a pathway for standardizing T1p as a quantitative biomarker for osteoarthritis.

Leukocyte-Poor Platelet-Rich Plasma Injections Improve Cartilage T1ρ and T2 and Patient-Reported Outcomes in Mild-to-Moderate Knee Osteoarthritis.

Purpose: To use T1ρ and T2 magnetic resonance imaging to evaluate the effect of leukocyte-poor platelet-rich plasma (LP-PRP) injections on knee cartilage health and to correlate structural changes with patient-reported outcome measurements. Methods: Ten patients with symptomatic unilateral mild-to-moderate knee osteoarthritis (Kellgren-Lawrence Grade 1-2) underwent T1ρ and T2 magnetic resonance imaging of both the symptomatic and contralateral knee before injection and 6 months after injection with LP-PRP. Patient-reported outcome questionnaires (Knee Osteoarthritis Outcome Score and International Knee Documentation Committee) that evaluate the domains of pain, symptoms, activities of daily living, sports function, and quality of life were completed at baseline, 3 months, 6 months, and 12 months after injection. T1ρ and T2 relaxation times, which are correlated with the proteoglycan and collagen concentration of cartilage, were measured in compartments with and without chondral lesions. Results: Ten patients were prospectively enrolled (9 female, 1 male) with a mean age of 52.9 years (range, 42-68) years and mean body mass index of 23.2 ± 1.9. Significant increases in Knee Osteoarthritis Outcome Score for all subscales and International Knee Documentation Committee scores were observed 3 months after injection and the improvements were sustained at 12 months. T1ρ and T2 values of compartments with chondral lesions were observed to significantly decrease by 6.0% (P = .036) and 7.1% (P = .017) 6 months after LP-PRP injection, respectively. No significant associations between T1ρ and T2 relaxation times and improvement in patient-reported outcomes were observed. Conclusions: Patients undergoing LP-PRP injections for the treatment of mild-to-moderate knee osteoarthritis had increased proteoglycan and collagen deposition in the cartilage of affected compartments by 6 months after injection. Patient-reported outcomes scores improved 3 months after injection and were sustained through 1 year after injection, but these improvements were not associated with the changes in proteoglycan and collagen deposition in knee cartilage. Level of Evidence: Level II, prospective cohort study.

A Longitudinal Cohort Study of Factors Impacting Healthcare Worker Burnout in New York City During the COVID-19 Pandemic.

OBJECTIVE: This study aimed to longitudinally examine the prevalence and correlates of burnout in frontline healthcare workers (FHCWs) during COVID-19 in New York City. METHODS: A prospective cohort study of 786 FHCWs at Mount Sinai Hospital was conducted during the initial COVID surge in April to May 2020 (T1) and November 2020 to January 2021 (T2) to assess factors impacting burnout. RESULTS: Burnout increased from 38.9% to 44.8% ( P = 0.002); 222 FHCWs (28.3%) had persistent burnout, 82 (10.5%) had early burnout, and 129 (16.5%) had delayed burnout. Relative to FHCWs with no burnout ( n = 350; 44.7%), those with persistent burnout reported more prepandemic burnout (relative risk [RR], 6.67), less value by supervisors (RR, 1.79), and lower optimism (RR, 0.82), whereas FHCWs with delayed burnout reported more prepandemic burnout (RR, 1.75) and caring for patients who died (RR, 3.12). CONCLUSION: FHCW burnout may be mitigated through increasing their sense of value, support, and optimism; treating mental health symptoms; and counseling regarding workplace distress.

Restriction spectrum imaging with elastic image registration for automated evaluation of response to neoadjuvant therapy in breast cancer.

Purpose: Dynamic contrast-enhanced MRI (DCE) and apparent diffusion coefficient (ADC) are currently used to evaluate treatment response of breast cancer. The purpose of the current study was to evaluate the three-component Restriction Spectrum Imaging model (RSI3C), a recent diffusion-weighted MRI (DWI)-based tumor classification method, combined with elastic image registration, to automatically monitor breast tumor size throughout neoadjuvant therapy. Experimental design: Breast cancer patients (n=27) underwent multi-parametric 3T MRI at four time points during treatment. Elastically-registered DWI images were used to generate an automatic RSI3C response classifier, assessed against manual DCE tumor size measurements and mean ADC values. Predictions of therapy response during treatment and residual tumor post-treatment were assessed using non-pathological complete response (non-pCR) as an endpoint. Results: Ten patients experienced pCR. Prediction of non-pCR using ROC AUC (95% CI) for change in measured tumor size from pre-treatment time point to early-treatment time point was 0.65 (0.38-0.92) for the RSI3C classifier, 0.64 (0.36-0.91) for DCE, and 0.45 (0.16-0.75) for change in mean ADC. Sensitivity for detection of residual disease post-treatment was 0.71 (0.44-0.90) for the RSI3C classifier, compared to 0.88 (0.64-0.99) for DCE and 0.76 (0.50-0.93) for ADC. Specificity was 0.90 (0.56-1.00) for the RSI3C classifier, 0.70 (0.35-0.93) for DCE, and 0.50 (0.19-0.81) for ADC. Conclusion: The automatic RSI3C classifier with elastic image registration suggested prediction of response to treatment after only three weeks, and showed performance comparable to DCE for assessment of residual tumor post-therapy. RSI3C may guide clinical decision-making and enable tailored treatment regimens and cost-efficient evaluation of neoadjuvant therapy of breast cancer.

How Medicare Advantage plans use data for supplemental benefits decision-making.

OBJECTIVES: Health care payers are increasingly experimenting with interventions to address social risk factors. With enactment of the 2018 Bipartisan Budget Act, Medicare Advantage (MA) plans have new opportunities to offer supplemental benefits that are not "primarily health-related." This article presents findings from interviews conducted with executives from MA plans regarding plan decision-making processes related to new social risk factor benefits. STUDY DESIGN: Semistructured qualitative interviews with MA plan leadership. METHODS: A total of 63 plan representatives from 29 unique MA plans were interviewed about the rationale for social risk-related interventions and how data are used to inform benefits expansion decisions. This paper combines qualitative interview data from 2 separate studies with similar target groups and interview guides. Interview transcripts were qualitatively analyzed to examine underlying themes. RESULTS: Three main themes emerged: (1) Plans use multiple data sources to determine how to target benefits; (2) evidence gaps hinder decision-making to expand or offer new supplemental benefits; and (3) in the absence of sufficient evidence, some plans have their own research and quality improvement processes to maximize effectiveness. CONCLUSIONS: Findings provide insights about opportunities and challenges that MA plans face in making decisions related to supplemental benefits designed to address members' social risk factors. Barriers include collecting, generating, and analyzing data critical to informing investments. Results highlight the need to ensure interoperability of new and existing data sources, foster shared learning opportunities, and narrow evidence gaps about specific social care interventions to inform the design and implementation of effective supplemental benefits.

Tri-Compartmental Restriction Spectrum Imaging Breast Model Distinguishes Malignant Lesions from Benign Lesions and Healthy Tissue on Diffusion-Weighted Imaging.

Diffusion-weighted MRI (DW-MRI) offers a potential adjunct to dynamic contrast-enhanced MRI to discriminate benign from malignant breast lesions by yielding quantitative information about tissue microstructure. Multi-component modeling of the DW-MRI signal over an extended b-value range (up to 3000 s/mm2) theoretically isolates the slowly diffusing (restricted) water component in tissues. Previously, a three-component restriction spectrum imaging (RSI) model demonstrated the ability to distinguish malignant lesions from healthy breast tissue. We further evaluated the utility of this three-component model to differentiate malignant from benign lesions and healthy tissue in 12 patients with known malignancy and synchronous pathology-proven benign lesions. The signal contributions from three distinct diffusion compartments were measured to generate parametric maps corresponding to diffusivity on a voxel-wise basis. The three-component model discriminated malignant from benign and healthy tissue, particularly using the restricted diffusion C1 compartment and product of the restricted and intermediate diffusion compartments (C1 and C2). However, benign lesions and healthy tissue did not significantly differ in diffusion characteristics. Quantitative discrimination of these three tissue types (malignant, benign, and healthy) in non-pre-defined lesions may enhance the clinical utility of DW-MRI in reducing excessive biopsies and aiding in surveillance and surgical evaluation without repeated exposure to gadolinium contrast.