Utility of Magnetic Resonance Imaging for Localizing Prostate Cancer Near the Urethra in Men Who Are Candidates for Focal Gland Ablation.

PURPOSE: Given that treatment near the urethra is often limited to reduce side effects, in this study we aim to determine whether prostate MRI can accurately identify the distance of prostate cancer to the urethra in a cohort of men who were potential candidates for focal gland ablation. MATERIALS AND METHODS: A single-institution analysis was performed of men who underwent MRI, targeted biopsy, and radical prostatectomy from July 2012 to April 2021. Men who were candidates for focal gland ablation were identified. The ability of MRI to identify prostate cancer within 5 mm of the prostatic urethra as confirmed on whole-mount pathology was assessed. Multivariate regression was utilized to determine characteristics associated with prostate cancer within 5 mm of the urethra on whole-mount pathology. RESULTS: In 48 out of 67 men (72%), the tumor was within 5 mm of the urethra on whole-mount pathology. MRI was concordant with whole-mount pathology in 49 out of 67 men (73%). The sensitivity of MRI for identifying cancer within 5 mm of the urethra was 77% (65%-89%) and the specificity was 63% (42%-89%). The positive predictive value was 84% (range 73%-95%) and negative predictive value was 52% (32%-73%). In adjusted analysis, PSA density and Prostate Imaging-Reporting and Data System were not significantly associated with having prostate cancer within close proximity of the urethra. CONCLUSIONS: A significant number of men who are potential candidates for focal gland ablation have cancer within close proximity to the urethra that could serve as a significant source of in-field recurrence. The sensitivity of MRI for identifying these lesions is 77% and can be used to further improve patient selection for focal gland ablation.

Magnetic Resonance Imaging-Guided Biopsy in Active Surveillance of Prostate Cancer.

PURPOSE: The underlying premise of prostate cancer active surveillance (AS) is that cancers likely to metastasize will be recognized and eliminated before cancer-related disease can ensue. Our study was designed to determine the prostate cancer upgrading rate when biopsy guided by magnetic resonance imaging (MRGBx) is used before entry and during AS. MATERIALS AND METHODS: The cohort included 519 men with low- or intermediate-risk prostate cancer who enrolled in prospective studies (NCT00949819 and NCT00102544) between February 2008 and February 2020. Subjects were preliminarily diagnosed with Gleason Grade Group (GG) 1 cancer; AS began when subsequent MRGBx confirmed GG1 or GG2. Participants underwent confirmatory MRGBx (targeted and systematic) followed by surveillance MRGBx approximately every 12 to 24 months. The primary outcome was tumor upgrading to ≥GG3. RESULTS: Upgrading to ≥GG3 was found in 92 men after a median followup of 4.8 years (IQR 3.1-6.5) after confirmatory MRGBx. Upgrade-free probability after 5 years was 0.85 (95% CI 0.81-0.88). Cancer detected in a magnetic resonance imaging lesion at confirmatory MRGBx increased risk of subsequent upgrading during AS (HR 2.8; 95% CI 1.3-6.0), as did presence of GG2 (HR 2.9; 95% CI 1.1-8.2) In men who upgraded ≥GG3 during AS, upgrading was detected by targeted cores only in 27%, systematic cores only in 25% and both in 47%. In 63 men undergoing prostatectomy, upgrading from MRGBx was found in only 5 (8%). CONCLUSIONS: When AS begins and follows with MRGBx (targeted and systematic), upgrading rate (≥GG3) is greater when tumor is initially present within a magnetic resonance imaging lesion or when pathology is GG2 than when these features are absent.

High-Resolution 3-T Endorectal Prostate MRI: A Multireader Study of Radiologist Preference and Perceived Interpretive Quality of 2D and 3D T2-Weighted Fast Spin-Echo MR Images.

OBJECTIVE: The goal of this study was to compare the perceived quality of 3-T axial T2-weighted high-resolution 2D and high-resolution 3D fast spin-echo (FSE) endorectal MR images of the prostate. MATERIALS AND METHODS: Six radiologists independently reviewed paired 3-T axial T2-weighted high-resolution 2D and 3D FSE endorectal MR images of the prostates of 85 men in two sessions. In the first session (n = 85), each reader selected his or her preferred images; in the second session (n = 28), they determined their confidence in tumor identification and compared the depiction of the prostatic anatomy, tumor conspicuity, and subjective intrinsic image quality of images. A meta-analysis using a random-effects model, logistic regression, and the paired Wilcoxon rank-sum test were used for statistical analyses. RESULTS: Three readers preferred the 2D acquisition (67-89%), and the other three preferred the 3D images (70-80%). The option for one of the techniques was not associated with any of the predictor variables. The 2D FSE images were significantly sharper than 3D FSE (p < 0.001) and significantly more likely to exhibit other (nonmotion) artifacts (p = 0.002). No other statistically significant differences were found. CONCLUSION: Our results suggest that there are strong individual preferences for the 2D or 3D FSE MR images, but there was a wide variability among radiologists. There were differences in image quality (image sharpness and presence of artifacts not related to motion) but not in the sequences' ability to delineate the glandular anatomy and depict a cancerous tumor.

Abdominal imaging can misdiagnose submassive hepatic necrosis as cirrhosis in acute liver failure.

Patients with acute liver failure (ALF) can be listed status I for liver transplantation (LT) whereas patients with cirrhosis must follow the MELD scoring system. Liver imaging can mistakenly diagnose submassive hepatic necrosis in ALF as cirrhosis. The purpose of our study was to assess the accuracy of ultrasound (US) and computed tomography (CT) in distinguishing cirrhosis from ALF. All patients listed for ALF and transplanted during the study period were included. Controls were age- and gender-matched cirrhotic patients who underwent LT during the same period. Abdominal US or CT scans obtained on all patients were independently reviewed by three blinded abdominal radiologists. Explants from all patients were reviewed by two blinded pathologists, and histological diagnosis was correlated with radiological diagnosis. Forty-one patients with ALF and 42 patients with cirrhosis were analyzed. Univariate and multivariate analyses both revealed overall accuracy of 85% for ultrasound and 93% for CT. US and CT scans both provide high levels of accuracy in terms of discriminating ALF from cirrhosis but measures taken to determine whether a patient has ALF vs. cirrhosis needs to approach 100% accuracy. Thus, imaging studies alone should not definitively diagnosis one etiology of liver failure over the other.

Role of endorectal magnetic resonance spectroscopic imaging in two different Gleason scores in prostate cancer.

OBJECTIVE: The major goal of the work was to record three-dimensional magnetic resonance spectroscopic imaging (MRSI) and to compare metabolite ratios between different Gleason scores (GS). MATERIALS AND METHODS: MRSI localized by endorectal coil-acquired point-resolved spectroscopy was performed in 14 men with prostate cancer of GS 6 (n = 7) and 7 (n = 7) using a 1.5-tesla MRI scanner. RESULTS: The ratio of (choline + creatine)/citrate was increased with an increase of GS, i.e. 0.590 ± 0.171 in the target lesion and 0.321 ± 0.157 in the contralateral region of patients with a GS of 6 as opposed to 1.082 ± 0.432 in the target lesion and 0.360 ± 0.243 in the contralateral region of patients with a GS of 7. CONCLUSION: Our pilot results demonstrated that MRSI was an additional biochemical tool which is complementary to the current imaging modalities for early diagnosis and therapeutic management of prostate cancer.

Correlation of endorectal 2D JPRESS findings with pathological Gleason scores in prostate cancer patients.

To determine the metabolite ratios of (Cho + Cr)/Cit and (Cho + Cr)/Spm in patients with two ranges of pathological Gleason scores, namely (3 + 4) and (4 + 3). By using the localized two-dimensional (2D) J-resolved spectroscopy (JPRESS) technique, the metabolites ratios can be calculated and correlated with prostate cancer aggressiveness. A total of 24 patients who underwent endorectal 2D JPRESS between April 2006 and July 2007 were included in this study. The 2D JPRESS voxel was localized predominantly in the peripheral zone suspected for malignancy based on pathology. Using the metabolites such as total choline (Cho), creatine (Cr), spermine (Spm) and citrate (Cit), the ratios (Cho + Cr)/Cit and (Cho + Cr)/Spm were calculated. In 14 prostate cancer patients who had a final pathologic Gleason scores of i) (3 + 4 = 7, n = 7) and ii) (4 + 3 = 7, n = 7), the metabolite ratios (mean +/- SD) of (Cho + Cr)/Cit and (Cho + Cr)/Spm were calculated using the 2D JPRESS spectra as follows: i) (1.48 +/- 0.83) and (1.59 +/- 0.73); ii) (2.90 +/- 0.94) and (2.71 +/- 1.47), respectively. Higher percentage of aggressive disease correlates with higher metabolites ratio. Our pilot study suggests that 2D JPRESS can be reliably evaluated in a clinical setting using an endorectal coil. In addition to the citrate ratio, the spermine ratio also correlates with pathology based Gleason score.

Noninvasive assessment of abdominal adipose tissues and quantification of hepatic and pancreatic fat fractions in type 2 diabetes mellitus.

The purpose of this study was to evaluate adipose tissue distributions and hepatic and pancreatic fat contents using a 6-point Dixon MRI technique in type 2 diabetes mellitus (T2DM), and to assess associations between fat distributions and biochemical markers of insulin resistance. Intra-abdominal MRI was investigated in 14 T2DM patients, 13 age- and sex-matched healthy controls (HC) and 11 young HC using a 3 T Prisma MRI scanner. All T2DM subjects completed a fasting comprehensive metabolic panel, and demographic measurements were taken according to standardized methodologies. We observed excellent correlation (R2 = 0.94) between hepatic fat fraction quantified using 6-point Dixon MRI and gold standard MRS, establishing the accuracy and reliability of the Dixon technique. Significantly increased visceral adipose tissue (VAT) volumes were found in T2DM patients compared to age-matched HC (1569.81 ± 670.62 cm3 vs. 1106.60 ± 566.85 cm3, p = .04). We also observed a trend of increasing subcutaneous adipose tissues (SAT), and total abdominal fat (TAT) volumes in T2DM compared to age-matched HC. Hepatic fat fraction percentage (HFF%) was 44.6% higher in T2DM compared to age-matched HC and 64.4% higher compared to young HC. Pancreatic fat fractions in the head and body/tail were higher in T2DM patients compared to both healthy cohorts. We also observed correlations between fat contents of the liver and pancreas in T2DM patients, and association between biochemical markers of T2DM with HFF, indicating a risk for non-alcoholic fatty liver disease among T2DM. In summary, this study provides evidence of T2DM patients having increased liver and pancreatic fat, as well as increased adipose tissues.

Three-dimensional mapping of gallbladder wall thickness on computed tomography using Laplace's equation.

RATIONALE AND OBJECTIVES: Traditionally, maximum gallbladder wall thickness is measured at a single point on ultrasonography. The purpose of this work was to develop an automated technique to measure the thickness of the gallbladder wall over the entire gallbladder surface using computer tomography (CT). MATERIALS AND METHODS: Subjects who had (5-mm) thick and thin (2.5-mm) reconstruction through the abdomen were selected from a research database. Their volumetric computed tomographic images were acquired using a multidetector GE Medical Systems LightSpeed 16 scanner at 120 kVp, approximately 250 mAs, with standard filter reconstruction algorithm and segmented in three dimensions. Two segmentation boundaries were obtained, an inner and an outer boundary of the gallbladder wall. The thickness of the wall was quantified by computing the distance between the boundaries over the entire volume using Laplace's equation from mathematical physics. The distance between the surfaces is found by computing normalized gradients that form a vector field, representing tangent vectors along field lines connecting both boundaries. The Laplacian technique was compared with the well-known Euclidean distance transformation (EDT) technique that provides a three-dimensional Euclidean distance mapping between the two extracted surfaces. RESULTS: The technique was tested on 10 subjects who had thin- and thick-section computed tomographic datasets reconstructed from a single scan. The mean thickness for the thick- and thin-section CT using Laplace was 3.18 and 2.93 mm, respectively. The smooth transition between surfaces resulting from the Laplace technique resulted in a coefficient of variation that was less than 1% compared to EDT. CONCLUSIONS: EDT technique is very sensitive to imperfect segmentations, resulting in higher variation compared to the Laplacian technique. The smooth transition between surfaces makes the Laplacian technique more robust compared to EDT for the measurement of CT gallbladder thickness.

Diffusion-weighted imaging in cancer: physical foundations and applications of restriction spectrum imaging.

Diffusion-weighted imaging (DWI) has been at the forefront of cancer imaging since the early 2000s. Before its application in clinical oncology, this powerful technique had already achieved widespread recognition due to its utility in the diagnosis of cerebral infarction. Following this initial success, the ability of DWI to detect inherent tissue contrast began to be exploited in the field of oncology. Although the initial oncologic applications for tumor detection and characterization, assessing treatment response, and predicting survival were primarily in the field of neurooncology, the scope of DWI has since broadened to include oncologic imaging of the prostate gland, breast, and liver. Despite its growing success and application, misconceptions about the underlying physical basis of the DWI signal exist among researchers and clinicians alike. In this review, we provide a detailed explanation of the biophysical basis of diffusion contrast, emphasizing the difference between hindered and restricted diffusion, and elucidating how diffusion parameters in tissue are derived from the measurements via the diffusion model. We describe one advanced DWI modeling technique, called restriction spectrum imaging (RSI). This technique offers a more direct in vivo measure of tumor cells, due to its ability to distinguish separable pools of water within tissue based on their intrinsic diffusion characteristics. Using RSI as an example, we then highlight the ability of advanced DWI techniques to address key clinical challenges in neurooncology, including improved tumor conspicuity, distinguishing actual response to therapy from pseudoresponse, and delineation of white matter tracts in regions of peritumoral edema. We also discuss how RSI, combined with new methods for correction of spatial distortions inherent in diffusion MRI scans, may enable more precise spatial targeting of lesions, with implications for radiation oncology and surgical planning. See all articles in this Cancer Research section, "Physics in Cancer Research."

Fine-tuning robot-assisted radical prostatectomy planning with MRI.

OBJECTIVES: Robot-assisted radical prostatectomy (RARP) has now become the most common surgical treatment option for prostate cancer (CaP). Clinicopathologic data (i.e., biopsy, digital rectal exam, prostate specific antigen level) and patient-specific factors (e.g., age, erectile function, co-morbidities) are the primary sources of information that urologists use for counseling and treatment decision making. Magnetic resonance imaging (MRI) has evolved along a similar temporal arc to RARP, with increased utilization and precision over the past decade. MRI prior to RARP provides multifaceted adjunctive information, including enhancement of locoregional staging, delineation of spatial anatomic information, and identification of aberrant anatomy, all of which aid in patient treatment counseling and operative planning. This article is designed for urologic surgeons who perform RARP, with the aim of providing a review of prostate MRI imaging and highlighting findings which may specifically alter the operation. METHODS AND MATERIALS: A review of the literature was performed, focusing on the most recent publications. RESULTS: MRI imaging of the prostate has become increasing accurate for the identification, localization, and characterization of CaP lesions. In addition to tumor-specific information, a number of intra- and extra-prostatic findings are consistently identified on MRI which may impact RARP. CONCLUSIONS: MRI provides important information which may alter RARP.

Diffusion tensor magnetic resonance tractography of the prostate: feasibility for mapping periprostatic fibers.

OBJECTIVE: To evaluate the feasibility of diffusion tensor imaging (DTI) tractography of the prostate for mapping of periprostatic neurovascular anatomy. METHODS: Eight men with prostate cancer scheduled to undergo nerve-sparing robot-assisted radical prostatectomy (RARP) underwent endorectal multiparametric magnetic resonance imaging (MRI) of the prostate with DTI. Tract mapping was accomplished by positioning spherical regions of interest contiguously along the prostatic capsule at the prostatic apex, midgland, and base. RESULTS: DTI tractography of the prostate effectively visualized periprostatic fiber tract anatomy. There was no significant correlation between total tract number and prostate size, however (Spearman's coefficient = 0.33, P = .42). Variation in tract distribution existed. The total fiber mass was highest in the lower prostate hemisphere at the base of the prostate (mean = 36.9 vs 21.1, P = .0004) and in the upper hemisphere at the apex (mean = 41.6 vs 57.9, P = .006). CONCLUSION: DTI tractography successfully visualized fiber tracts around the prostate. Gold standard anatomic correlation is needed.

Intra-lymph node prime-boost vaccination against Melan A and tyrosinase for the treatment of metastatic melanoma: results of a phase 1 clinical trial.

PURPOSE: The goal of this study was to test the safety and activity of a therapeutic vaccine, MKC1106-MT, in patients with metastatic melanoma. EXPERIMENTAL DESIGN: MKC1106-MT comprises a plasmid (pMEL-TYR) and two peptides (E-MEL and E-TYR), corresponding to Melan A and tyrosinase, administered by intra-lymph node injection in a prime-boost sequence. All 18 patients were HLA-A*0201 positive and received a fixed priming dose of plasmid and a low or a high peptide dose. Enumeration of antigen-specific T cells was done prior to and throughout the treatment. Patients who did not exhibit disease progression remained on study and could receive up to eight cycles of treatment. RESULTS: The MKC1106-MT regimen was well tolerated and resulted in an overall immune response rate of 50%. The treatment showed disease control, defined as stable disease that lasted for 8 weeks or more in 6 of 18 (33%) of the patients: 14% and 46% in the low and high peptide dose, respectively. Interestingly, four patients, all with tumor burden largely confined to lymph nodes and Melan A-specific T cells at baseline, showed durable disease control associated with radiologic evidence of tumor regression. There was no noticeable correlation between the expansion of antigen-specific T cells in blood and the clinical outcome; yet, there was evidence of active tumor-infiltrating lymphocytes (TIL) in two regressing lesions. CONCLUSIONS: MKC1106-MT showed immunogenicity and evidence of disease control in a defined patient population. These findings support further development of this investigational agent and the concept of therapeutic vaccination in metastatic melanoma.

Two-dimensional MR spectroscopy of healthy and cancerous prostates in vivo.

OBJECTIVES: A major goal of this article is to summarize the current status of evaluating prostate metabolites non-invasively using spatially resolved two-dimensional (2D) MR Spectroscopy (MRS). MATERIALS AND METHODS: Due to various technical challenges, the spatially resolved versions of 2D MRS techniques are currently going through the developmental stage. During the last decade, four different versions of 2D MRS sequences have been successfully implemented on 3T and 1.5T MRI scanners manufactured by three different vendors. These sequences include half and maximum echo sampled J-resolved spectroscopy (JPRESS), S-PRESS and L-COSY, which are single volume localizing sequences, and the multi-voxel based JPRESS sequence. RESULTS: Even though greater than 1ml voxels have been used, preliminary evaluations of 2D JPRESS, S-PRESS and L-COSY sequences have demonstrated unambiguous detection of citrate, creatine, choline, spermine and more metabolites in human prostates. ProFIT-based quantitation of JPRESS and L-COSY data clearly shows the superiority of 2D MRS over conventional one-dimensional (1D) MRS and more than six metabolites have been successfully quantified. These sequences have been evaluated in a small group of prostate pathologies and pilot investigations using these sequences show promising results in prostate pathologies. CONCLUSION: Implementation of the state-of-the-art 2D MRS techniques and preliminary evaluation in prostate pathologies are discussed in this review. Even though these techniques are going through developmental and early testing phases, it is evident that 2D MRS can be easily added on to any clinical Magnetic Resonance Imaging (MRI) protocol to non-invasively record the biochemical contents of the prostate.