A Novel Large Scale Integrated Telemonitoring Program for COVID-19.

Introduction: Coronavirus disease 2019 (COVID-19) has forced health care systems to rethink the optimal delivery of health care services and has dramatically increased demand for general medicine providers (internal medicine, family medicine, emergency medicine), while simultaneously reducing demand for many subspecialty services. At Kaiser Permanente, we implemented a program wherein health care providers drawn from multiple disciplines perform daily telemedicine check-ins on COVID-19 patients, allowing us to both maintain social distancing and make use of providers in specialties who otherwise may have had lower in-clinic volumes. Methods: Kaiser Permanente patients testing positive for COVID-19 between March and October 2020 were referred to our program. Physicians and nurses (RNs) were invited to participate in our program and were trained using Microsoft Teams™ meetings. Patients receive daily phone calls by a physician or RN. Select patients receive portable pulse oximeter devices based on standardized criteria incorporating age and comorbidities. When patients are determined to be clinically stable, they are discharged back to their primary care physician for ongoing management. Results: Descriptive results for the virtual home care program (VHCP) are reported through October 2020, though these results do not represent a planned statistical analysis. Forty-two percent of the patients were male, 43% were black, and 30% were Hispanic. The most common comorbidities of patients in our program were obesity (body mass index >30 kg/m2; 35%), followed by hypertension (32%) and diabetes mellitus (19%). Then, 8.2% of patients ultimately required hospital admission. Mortality rate for patients in our program was 1.33%. Discussion: Our program was able to provide virtual care for thousands of COVID-19 positive Kaiser members in the Washington, DC, and Baltimore Metro regions. We did so by utilizing physicians and RNs from specialties experiencing a decrease in clinic volume attributable to the COVID-19 pandemic. The experiences of our program may be valuable to clinicians wishing to establish similar programs of their own.

Prostate Cancer: A Correlative Study of Multiparametric MR Imaging and Digital Histopathology.

Purpose To correlate multiparametric magnetic resonance (MR) imaging and quantitative digital histopathologic analysis (DHA) of the prostate. Materials and Methods This retrospective study was approved by the local institutional review board and was HIPAA compliant. Forty patients (median age, 60 years; age range, 44-71 years) who underwent prostate MR imaging consisting of T2-weighted and diffusion-weighted (DW) MR imaging along with subsequent robot-assisted radical prostatectomy gave informed consent to be included. Whole-mount tissue specimens were obtained with a patient-specific mold, and DHA was performed to assess the lumen, epithelium, stroma, and epithelial nucleus. These DHA images were registered with MR images and were correlated on a per-voxel basis. The relationship between MR imaging and DHA was assessed by using a linear mixed-effects model and the Pearson correlation coefficient. Results T2-weighted MR imaging, apparent diffusion coefficient (ADC) of DW imaging, and high-b-value DW imaging were significantly related to specific DHA parameters (P < .01). For instance, lumen density (ie, the percentage area of tissue components) was associated with T2-weighted MR imaging (slope = 0.36 ± 0.05 [standard error], γ = 0.35), ADC (slope = 0.47 ± 0.05, γ = 0.50), and high-b-value DW imaging (slope = -0.44 ± 0.05, γ = -0.44). Differences between regions harboring benign tissue and those harboring malignant tissue were observed at MR imaging and DHA (P < .01). Gleason score was significantly associated with MR imaging and DHA parameters (P < .05). For example, it was positively related to high-b-value DW imaging (slope = 0.21 ± 0.16, γ = 0.18) and negatively related to lumen density (slope = -0.19 ± 0.18, γ = -0.35). Conclusion Overall, significant associations were observed between MR imaging and DHA, regardless of prostate anatomy. © RSNA, 2017 Online supplemental material is available for this article.

Accuracy and agreement of PIRADSv2 for prostate cancer mpMRI: A multireader study.

PURPOSE: Multiparametric MRI (mpMRI) improves the detection of clinically significant prostate cancer, but is limited by interobserver variation. The second version of theProstate Imaging Reporting and Data System (PIRADSv2) was recently proposed as a standard for interpreting mpMRI. To assess the performance and interobserver agreement of PIRADSv2 we performed a multi-reader study with five radiologists of varying experience. MATERIALS AND METHODS: Five radiologists (n = 2 prostate dedicated, n = 3 general body) blinded to clinicopathologic results detected and scored lesions on prostate mpMRI using PIRADSv2. The endorectal coil 3 Tesla MRI included T2W, diffusion-weighted imaging (apparent diffusion coefficient, b2000), and dynamic contrast enhancement. Thirty-four consecutive patients were included. Results were correlated with radical prostatectomy whole-mount histopathology produced with patient-specific three-dimensional molds. An index lesion was defined on pathology as the lesion with highest Gleason score or largest volume if equivalent grades. Average sensitivity and positive predictive values (PPVs) for all lesions and index lesions were determined using generalized estimating equations. Interobserver agreement was evaluated using index of specific agreement. RESULTS: Average sensitivity was 91% for detecting index lesions and 63% for all lesions across all readers. PPV was 85% for PIRADS ≥ 3 and 90% for PIRADS ≥ 4. Specialists performed better only for PIRADS ≥ 4 with sensitivity 90% versus 79% (P = 0.01) for index lesions. Index of specific agreement among readers was 93% for the detection of index lesions, 74% for the detection of all lesions, and 85% for scoring index lesions, and 58% for scoring all lesions. CONCLUSION: By using PIRADSv2, general body radiologists and prostate specialists can detect high-grade index prostate cancer lesions with high sensitivity and agreement. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:579-585.

Optimal high b-value for diffusion weighted MRI in diagnosing high risk prostate cancers in the peripheral zone.

PURPOSE: To retrospectively determine the optimal b-value(s) of diffusion-weighted imaging (DWI) associated with intermediate-high risk cancer in the peripheral zone (PZ) of the prostate. MATERIALS AND METHODS: Forty-two consecutive patients underwent multi b-value (16 evenly spaced b-values between 0 and 2000 s/mm2 ) DWI along with multi-parametric MRI (MP-MRI) of the prostate at 3 Tesla followed by trans-rectal ultrasound/MRI fusion guided targeted biopsy of suspicious lesions detected at MP-MRI. Computed DWI images up to a simulated b-value of 4000 s/mm2 were also obtained using a pair of b-values (b = 133 and 400 or 667 or 933 s/mm2 ) from the multi b-value DWI. The contrast ratio of average intensity of the targeted lesions and the background PZ was determined. Receiver operator characteristic curves and the area under the curve (AUCs) were obtained for separating patients eligible for active surveillance with low risk prostate cancers from intermediate-high risk prostate cancers as per the cancer of the prostate risk assessment (CAPRA) scoring system. RESULTS: The AUC first increased then decreased with the increase in b-values reaching maximum at b = 1600 s/mm2 (0.74) with no statistically significant different AUC of DWI with b-values 1067-2000 s/mm2 . The AUC of computed DWI increased then decreased with the increase in b-values reaching a maximum of 0.75 around b = 2000 s/mm2 . There was no statistically significant difference between the AUC of optimal acquired DWI and either of optimal computed DWI. CONCLUSION: The optimal b-value for acquired DWI in differentiating intermediate-high from low risk prostate cancers in the PZ is b = 1600 s/mm2 . The computed DWI has similar performance as that of acquired DWI with the optimal performance around b = 2000 s/mm2 . LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:125-131.

Application of an unsupervised multi-characteristic framework for intermediate-high risk prostate cancer localization using diffusion-weighted MRI.

PURPOSE: The aim of this proof-of-concept work is to propose an unsupervised framework that combines multiple parameters, in "positive-if-all-positive" manner, from different models to localize tumors. METHODS: A voxel-by-voxel analysis of the DW-MRI images of whole prostate was performed to obtain parametric maps for D*, D, f, and K using the IVIM and kurtosis models. Ten patients with moderate or high-risk prostate cancer were included in study. The mean age and serum PSA for these 10 patients were 65years (range 54-78) and 21.9ng/mL (range 4.84-44.81), respectively. These patients were scanned using a DW spin-echo sequence with echo-planar readout with 16 equidistantly spaced b-values in the range of 0-2000s/mm2 (TE=58ms; TR=3990ms; spatial resolution 2.19×2.19×2.73mm3, slices =26, FOV=140×140mm, slice gap =0.27mm, NSA=2). RESULTS: The proposed framework detected 24 lesions of which 14 were true positive with 58% tumor detection rate on lesion-based analysis with sensitivity of 100%. The mpMRI evaluation (PIRADSv2) identified 12 of 14 true positive lesions with sensitivity of 86%; positive predictive value of mpMRI was 92%. The index lesions were visible on all framework maps and were coded as the most suspicious in 9 of 10 patients. CONCLUSION: Preliminary results of the proposed framework indicate high patient-based sensitivity with 100% detection rate for identifying moderate-high risk aggressive index lesions.

Preoperative Multiparametric Magnetic Resonance Imaging Predicts Biochemical Recurrence in Prostate Cancer after Radical Prostatectomy.

OBJECTIVES: To evaluate the utility of preoperative multiparametric magnetic resonance imaging (MP-MRI) in predicting biochemical recurrence (BCR) following radical prostatectomy (RP). MATERIALS/METHODS: From March 2007 to January 2015, 421 consecutive patients with prostate cancer (PCa) underwent preoperative MP-MRI and RP. BCR-free survival rates were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to identify clinical and imaging variables predictive of BCR. Logistic regression was performed to generate a nomogram to predict three-year BCR probability. RESULTS: Of the total cohort, 370 patients met inclusion criteria with 39 (10.5%) patients experiencing BCR. On multivariate analysis, preoperative prostate-specific antigen (PSA) (p = 0.01), biopsy Gleason score (p = 0.0008), MP-MRI suspicion score (p = 0.03), and extracapsular extension on MP-MRI (p = 0.03) were significantly associated with time to BCR. A nomogram integrating these factors to predict BCR at three years after RP demonstrated a c-index of 0.84, outperforming the predictive value of Gleason score and PSA alone (c-index 0.74, p = 0.02). CONCLUSION: The addition of MP-MRI to standard clinical factors significantly improves prediction of BCR in a post-prostatectomy PCa cohort. This could serve as a valuable tool to support clinical decision-making in patients with moderate and high-risk cancers.

DCE MRI of prostate cancer.

DCE MRI is an established component of multi-parametric MRI of the prostate. The sequence highlights the vascularization of cancerous lesions, allowing readers to corroborate suspicious findings on T2W and DW MRI and to note subtle lesions not visible on the other sequences. In this article, we review the technical aspects, methods of evaluation, limitations, and future perspectives of DCE MRI.

Differentiating Transition Zone Cancers From Benign Prostatic Hyperplasia by Quantitative Multiparametric Magnetic Resonance Imaging.

OBJECTIVE: The aim of this study was to evaluate the value of quantitative diffusion and perfusion parameters to aid in discriminating between transition zone carcinomas and benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Twenty-four transition zone cancers and BPH nodules were contoured on T2-weighted magnetic resonance imaging (MRI), apparent diffusion coefficient (ADC) maps, and raw dynamic contrast-enhanced (DCE) MRI. Benign prostatic hyperplasia nodules were then stratified into 2 groups based on the presence or absence of a capsule. Apparent diffusion coefficient values, per-voxel Ktrans, kep, vp, and ve were all compared across all groups. RESULTS: Average ADCs (×10 mm/s) were 1019.22, 1338.11, and 1272.46 for cancer, encapsulated BPH, and nonencapsulated BPH, respectively. Both subgroups of BPH were found to be significantly different than that of cancer (P < 0.05). No individual DCE-MRI parameter was significantly different between cancer and either BPH group. The area under the curve for ADC alone was 0.83, and no individual DCE imaging parameter improved the area under the curve of ADC. CONCLUSIONS: Apparent diffusion coefficient may play a role in distinguishing TZ cancers from non-encapsulated BPH nodules that closely resemble cancer.

Multiparametric prostate magnetic resonance imaging in the evaluation of prostate cancer.

Imaging has traditionally played a minor role in the diagnosis and staging of prostate cancer. However, recent controversies generated by the use of prostate-specific antigen (PSA) screening followed by random biopsy have encouraged the development of new imaging methods for prostate cancer. Multiparametric magnetic resonance imaging (mpMRI) has emerged as the imaging method best able to detect clinically significant prostate cancers and to guide biopsies. Here, the authors explain what mpMRI is and how it is used clinically, especially with regard to high-risk populations, and we discuss the impact of mpMRI on treatment decisions for men with prostate cancer. CA Cancer J Clin 2016;66:326-336. © 2015 American Cancer Society.

Combined Biparametric Prostate Magnetic Resonance Imaging and Prostate-specific Antigen in the Detection of Prostate Cancer: A Validation Study in a Biopsy-naive Patient Population.

OBJECTIVE: To validate the use of biparametric (T2- and diffusion-weighted) magnetic resonance imaging (B-MRI) and prostate-specific antigen (PSA) or PSA density (PSAD) in a biopsy-naive cohort at risk for prostate cancer (PCa). METHODS: All patients (n = 59) underwent PSA screening and digital rectal exam prior to a B-MRI followed by MRI or transrectal ultrasound fusion-guided targeted biopsy. Previously reported composite formulas incorporating screen positive lesions (SPL) on B-MRI and PSA or PSAD were developed to maximize PCa detection. For PSA, a patient was considered screen positive if PSA level + 6 × (the number of SPL) >14. For PSAD, screening was positive if PSAD × 14 + (the number of SPL) >4.25. These schemes were employed in this new test set to validate the initial formulas. Performance assessment of these formulas was determined for all cancer detection and for tumors with Gleason ≥3 + 4. RESULTS: Screen positive lesions on B-MRI had the highest sensitivity (95.5%) and negative predictive value of 71.4% compared with PSA and PSAD. B-MRI significantly improved sensitivity (43.2-72.7%, P = .0002) when combined with PSAD. The negative predictive value of PSA increased with B-MRI, achieving 91.7% for B-MRI and PSA for Gleason ≥3 + 4. Overall accuracies of the composite equations were 81.4% (B-MRI and PSA) and 78.0% (B-MRI and PSAD). CONCLUSION: Validation with a biopsy-naive cohort demonstrates the parameter SPL performed better than PSA or PSAD alone in accurately detecting PCa. The combined use of B-MRI, PSA, and PSAD resulted in improved accuracy for detecting clinically significant PCa.

Correlation of magnetic resonance imaging with digital histopathology in prostate.

PURPOSE: We propose a systematic approach to correlate MRI and digital histopathology in prostate. METHODS: T2-weighted (T2W) MRI and diffusion-weighted imaging (DWI) are acquired, and a patient-specific mold (PSM) is designed from the MRI. Following prostatectomy, a whole mount tissue specimen is placed in the PSM and sectioned, ensuring that tissue blocks roughly correspond to MRI slices. Rigid body and thin plate spline deformable registration attempt to correct deformation during image acquisition and tissue preparation and achieve a more complete one-to-one correspondence between MRIs and tissue sections. Each tissue section is stained with hematoxylin and eosin and segmented by adopting a machine learning approach. Utilizing this tissue segmentation and image registration, the density of cellular and tissue components (lumen, nucleus, epithelium, and stroma) is estimated per MR voxel, generating density maps for the whole prostate. RESULTS: This study was approved by the local IRB, and informed consent was obtained from all patients. Registration of tissue specimens and MRIs was aided by the PSM and subsequent image registration. Tissue segmentation was performed using a machine learning approach, achieving ≥0.98 AUCs for lumen, nucleus, epithelium, and stroma. Examining the density map of tissue components, significant differences were observed between cancer, benign peripheral zone, and benign prostatic hyperplasia (p value <5e−2). Similarly, the signal intensity of the corresponding areas in both T2W MRI and DWI was significantly different (p value <1e−10). CONCLUSIONS: The proposed approach is able to correlate MRI and digital histopathology of the prostate and is promising as a potential tool to facilitate a more cellular and zonal tissue-based analysis of prostate MRI, based upon a correlative histopathology perspective.

Ferumoxytol as an intraprostatic MR contrast agent for lymph node mapping of the prostate: a feasibility study in non-human primates.

Background A variety of magnetic resonance (MR) lymphographic agents have been proposed for mapping the lymph nodes draining the prostate. Purpose To investigate the feasibility of using ferumoxytol (an FDA-approved iron oxide agent) for lymph node mapping of the prostate on imaging (MRI) in a non-human primate (NHP) Macaque model. Material and Methods Four NHPs weighing 5-13 kg underwent injection of ferumoxytol after a needle was introduced transrectally under MRI guidance into the prostate using a commercially available intrarectal MRI biopsy guide. Ferumoxytol was administered at dosage in the range of 0.15-0.75 mg Fe/kg in a fixed injection volume of 0.2 mL. T1-weighted MRI was performed at 3 T starting immediately and extending at least 45 min post-injection. Two readers evaluated the images in consensus. The NHPs tolerated the ferumoxytol injections at all doses with no evident side effects. Results It was determined that the lowest dose of 0.15 mg Fe/kg produced the best outcome in terms of lymph node visualization and draining nodes were reliably visualized at this dose and volume. Conclusion Thus, MRI with intraprostatic injection of ferumoxytol may be considered an effective T1 contrast agent for prospective mapping of lymph nodes draining the prostate and, thus, for attempted sentinel lymph node identification in prostate cancer. Large clinical trials to determine safety and efficacy are needed.

Imaging of renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common kidney cancer in adults. Early and accurate imaging plays an important role in the detection, staging, and follow-up of RCC. Patient care and case management revolves heavily around diagnostic imaging so it is imperative that appropriate and adequate imaging is acquired. There are well-established standard imaging protocols available to patients and their providers, although at the same time, there is also extensive ongoing research on improving the various modalities. Ultrasound has been the most commonly used imaging technique for renal imaging in general. However, computed tomography (CT) is the first choice for imaging of renal masses, and has been the mainstay for several decades. High resolution, reproducibility, reasonable preparation and acquisition time, and acceptable cost allow CT to remain as the primary choice for radiologic imaging. Magnetic resonance imaging (MRI) is considered as an important alternative in patients requiring further imaging or in cases of allergies, pregnancy, or surveillance. With increasing concern over radiation exposure, there has been a trend toward the higher use of MRI. It is important to understand the various imaging options available, as well as the current status of and results from recent RCC imaging studies. In this review we discuss these modalities, including the current state of ultrasound, CT, and MRI in RCC.

Does focal incidental 18F-FDG PET/CT uptake in the prostate have significance?

PURPOSE: (18)F-FDG PET/CT is used to characterize many malignancies, but is not recommended for localized prostate cancer. This study explores the value of multi-parametric MRI (mpMRI) in characterizing incidental prostate (18)F-FDG uptake. METHODS: Thirty-one patients who underwent (18)F-FDG PET/CT for reasons unrelated to prostate cancer and prostate mpMRI were eligible for this retrospective study. The mpMRI included T2-weighted (T2W), dynamic contrast enhancement (DCE), apparent diffusion coefficient (ADC), and MR spectroscopy (MRS) sequences. Fourteen patients were excluded (n = 8 insufficient histopathology, n = 6 radical prostatectomy before PET), and final analysis included 17 patients. A nuclear medicine physician, blinded to clinicopathologic findings, identified suspicious areas and maximum standardized uptake values (SUV max) on (18)F-FDG PET/CT. Sector-based imaging findings were correlated with annotated histopathology from whole-mount or MRI/transrectal ultrasound fusion biopsy samples. Positive predictive values (PPVs) were estimated using generalized estimating equations with logit link. Results were evaluated with Kruskal-Wallis and Dunn's multiple comparisons tests. RESULTS: The PPV of (18)F-FDG PET alone in detecting prostate cancer was 0.65. Combining (18)F-FDG PET as a base parameter with mpMRI (T2W, DCE, ADC, and MRS) increased the PPV to 0.82, 0.83, 0.83, and 0.94, respectively. All benign lesions had SUV max < 6. Malignant lesions had higher SUV max values that correlated with Gleason scores. There was a significant difference in SUV max per prostate between the Gleason ≥ 4 + 5 and benign categories (p = 0.03). CONCLUSIONS: Focal incidental prostate (18)F-FDG uptake has low clinical utility alone, but regions of uptake may harbor high-grade prostate cancer, especially if SUV max > 6. Using mpMRI to further evaluate incidental (18)F-FDG uptake aids the diagnosis of prostate cancer.

Multiparametric magnetic resonance imaging-transrectal ultrasound fusion-assisted biopsy for the diagnosis of local recurrence after radical prostatectomy.

OBJECTIVE: Approximately 15% of patients who undergo radical prostatectomy (RP) for prostate cancer develop local recurrence, which is heralded by a rise in serum prostate-specific antigen (PSA) levels. Early detection and treatment of recurrence improves the outcome of salvage treatment. We investigated the ability of multiparametric magnetic resonance imaging (mpMRI)-transrectal ultrasound (TRUS) fusion-guided biopsy (FGB) combined with "cognitive biopsy" to confirm local recurrence of prostate cancer after RP. MATERIALS AND METHODS: In this retrospective study conducted between January 2010 and December 2014, patients with rising PSA levels after RP who had no known evidence of distant metastases underwent mpMRI including T2-weighted (T2W) imaging, diffusion-weighted imaging, dynamic contrast-enhanced (DCE) MRI at 3 Tesla, and subsequent MRI-ultrasound fusion biopsy with cognitive assistance. The detection rate of locally recurrent disease was determined. RESULTS: A total of 10 patients (mean age = 67y, mean PSA level = 3.44ng/ml) met the inclusion criteria. Of the 10 patients, all had positive findings suspicious for local recurrence on mpMRI per entrance criterion. The most important features on mpMRI were early enhancement on DCE MR images and hypointensity on T2W images. The average lesion diameter on mpMRI was 1.12cm (range: 0.40-2.20cm). All suspicious lesions (16/16, 100%) were positive on T2W MR images, 14 (89%) showed positive features on apparent diffusion coefficient maps of diffusion-weighted images, and 16 (100%) were positive on DCE MR images. MRI-TRUS FGBs were positive in 10/16 lesions (62.5%) and 8/10 (80%) patients. CONCLUSION: MRI-TRUS FGB with cognitive assistance is able to detect and diagnose locally recurrent lesions after RP, even at low PSA levels. This may facilitate early detection of recurrent disease and improve salvage treatment outcomes.

Prostate Cancer: Interobserver Agreement and Accuracy with the Revised Prostate Imaging Reporting and Data System at Multiparametric MR Imaging.

PURPOSE: To evaluate accuracy and interobserver variability with the use of the Prostate Imaging Reporting and Data System (PI-RADS) version 2.0 for detection of prostate cancer at multiparametric magnetic resonance (MR) imaging in a biopsy-naïve patient population. MATERIALS AND METHODS: This retrospective HIPAA-compliant study was approved by the local ethics committee, and written informed consent was obtained from all patients for use of their imaging and histopathologic data in future research studies. In 101 biopsy-naïve patients with elevated prostate-specific antigen levels who underwent multiparametric MR imaging of the prostate and subsequent transrectal ultrasonography (US)-MR imaging fusion-guided biopsy, suspicious lesions detected at multiparametric MR imaging were scored by five readers who were blinded to pathologic results by using to the newly revised PI-RADS and the scoring system developed in-house. Interobserver agreement was evaluated by using κ statistics, and the correlation of pathologic results with each of the two scoring systems was evaluated by using the Kendall τ correlation coefficient. RESULTS: Specimens of 162 lesions in 94 patients were sampled by means of transrectal US-MR imaging fusion biopsy. Results for 87 (54%) lesions were positive for prostate cancer. Kendall τ values with the PI-RADS and the in-house-developed scoring system, respectively, at T2-weighted MR imaging in the peripheral zone were 0.51 and 0.17 and in the transitional zone, 0.45 and -0.11; at diffusion-weighted MR imaging, 0.42 and 0.28; at dynamic contrast material-enhanced MR imaging, 0.23 and 0.24, and overall suspicion scores were 0.42 and 0.49. Median κ scores among all possible pairs of readers for PI-RADS and the in-house-developed scoring system, respectively, for T2-weighted MR images in the peripheral zone were 0.47 and 0.15; transitional zone, 0.37 and 0.07; diffusion-weighted MR imaging, 0.41 and 0.57; dynamic contrast-enhanced MR imaging, 0.48 and 0.41; and overall suspicion scores, 0.46 and 0.55. CONCLUSION: Use of the revised PI-RADS provides moderately reproducible MR imaging scores for detection of clinically relevant disease.

A Phase I Dosing Study of Ferumoxytol for MR Lymphography at 3 T in Patients With Prostate Cancer.

OBJECTIVE: The objective of our study was to determine the optimal dose of ferumoxytol for performing MR lymphography (MRL) at 3 T in patients with prostate cancer. SUBJECTS AND METHODS: This phase I trial enrolled patients undergoing radical prostatectomy (RP) with bilateral pelvic lymph node dissection (PLND). Three groups of five patients each (total of 15 patients) received IV ferumoxytol before RP with bilateral PLND at each of the following doses of iron: 4, 6, and 7.5 mg Fe/kg. Patients underwent abdominopelvic MRI at 3 T before and 24 hours after ferumoxytol injection using T2- and T2*-weighted sequences. Normalized signal intensity (SI) and normalized SD changes from baseline to 24 hours after injection within visible lymph nodes were calculated for each dose level. Linear mixed effects models were used to estimate the effects of dose on the percentage SI change and log-transformed SD change within visible lymph nodes to determine the optimal dose of ferumoxytol for achieving uniform low SI in normal nodes. RESULTS: One patient who was excluded from the study group had a mild allergic reaction requiring treatment after approximately 2.5 mg Fe/kg ferumoxytol injection whereupon the injection was interrupted. The 15 study group patients tolerated ferumoxytol at all dose levels. The mean percentage SI change in 13 patients with no evidence of lymph metastasis was -36.4%, -45.4%, and -65.1% for 4, 6, and 7.5 mg Fe/kg doses, respectively (p = 0.041). CONCLUSION: A dose level of 7.5 mg Fe/kg ferumoxytol was safe and effective in deenhancing benign lymph nodes. This dose therefore can be the starting point for future phase II studies regarding the efficacy of ferumoxytol for MRL.

Posterior subcapsular prostate cancer: identification with mpMRI and MRI/TRUS fusion-guided biopsy.

PURPOSE: The posterior subcapsular region of the prostate is often undersampled by transrectal ultrasound (TRUS)-guided biopsy. The close proximity of these lesions to the posterior capsular wall of the prostate makes them difficult to localize while increasing the need for early detection because of their increased risk for extracapsular extension. We retrospectively evaluated the multiparametric MRI (mpMRI) features of subcapsular prostate cancers to make radiologists more aware of this condition. MATERIALS AND METHODS: Between January 2010 and July 2014, all patients referred for 3T mpMRI and subsequent MR-US Fusion-guided biopsy (FgBx) and systematic 12-core sextant biopsy (SBx) under an IRB approved protocol, were reviewed, and imaging confirmed subcapsular prostate cancers were identified. Subcapsular lesions were defined as thin lesions that were just inside the prostate capsule. Matching patient demographics and clinical findings including age, PSA, PSA density, whole prostate volume, history of prostate cancer, Gleason score, and clinical management were tabulated. RESULTS: Of 992 eligible patients, 33 patients had subcapsular lesions in the prostate detected by mpMRI. Mean age, PSA, and prostate volume in this group were 63 years (range: 52-76 years), 8.4 ng/mL (range: 1.22-65.20), and 53 mL (range: 12-125 mL), respectively. The combination biopsy (SBx + FgBx) confirmed prostate cancer in 24 of 33 patients (72.7%) and in 9 patients the biopsy was negative. Of the 24 cancers, 19 were confirmed on both FgBx and conventional biopsy; however, 5 cancers were only detected on FgBx. In 4 of the 19 patients in which both biopsy methods were positive, the FgBx yielded a higher Gleason score. CONCLUSION: Subcapsular lesions on mpMRI are relatively infrequent but are usually malignant. Although the majority are confirmed on conventional 12-core biopsies, about 20% of these lesions require FgBx for diagnosis, and FgBx more accurately grades the lesions in another 20%. Thus, FgBx is of considerable benefit in confirming the diagnosis of subcapsular prostate cancer despite their proximity to the prostatic capsule.

Lymph node staging in prostate cancer.

Nodal staging is important in prostate cancer treatment. While surgical lymph node dissection is the classic method of determining whether lymph nodes harbor malignancy, this is a very invasive technique. Current noninvasive approaches to identifying malignant lymph nodes are limited. Conventional imaging methods rely on size and morphology of lymph nodes and have notoriously low sensitivity for detecting malignant nodes. New imaging techniques such as targeted positron emission tomography (PET) imaging and magnetic resonance lymphography (MRL) with iron oxide particles are promising for nodal staging of prostate cancer. In this review, the strengths and limitations of imaging techniques for lymph node staging of prostate cancer are discussed.

Magnetic resonance sentinel lymph node imaging of the prostate with gadofosveset trisodium-albumin: preliminary results in a canine model.

RATIONALE AND OBJECTIVES: To determine if intraprostatic injection of gadofosveset trisodium mixed with human serum albumin (HSA) can identify sentinel lymph nodes (LNs) draining the prostate on magnetic resonance imaging (MRI) in a canine model. MATERIALS AND METHODS: Three male canines weighing between 25.7 and 41.3 kg were anesthetized, placed in a 3-T MRI, and a needle was placed transrectally into one side of the prostate using a commercially available intrarectal needle guide. Gadofosveset trisodium premixed with 10% HSA was then administered at doses ranging from 0.1 to 2.5 mL. T1W MRI was performed immediately after injection, and two readers evaluated images for visualization of LNs draining the prostate. RESULTS: Intraprostatic injection of 0.2 mL gadofosveset trisodium premixed with HSA identified the draining periprostatic LNs in all cases. Delayed images demonstrated upper echelon nodes in the pelvis and the abdomen. Higher volume injections resulted in excessive periprostatic extravasation, whereas lower volume injections resulted in suboptimal visualization of LNs. CONCLUSIONS: We demonstrate that gadofosveset trisodium (premixed with 10% HSA) injected intraprostatically at 0.2 mL visualized LNs draining the prostate. This approach can be readily adapted for clinical applications such as sentinel LN imaging in prostate cancer patients before surgery.