Multi-echo single-shot spectroscopy combined with simultaneous 2D model fitting for fast and accurate measurement of metabolite-specific concentrations and T2 relaxation times.

The purpose of the current study was to develop a novel single-voxel MR spectroscopy acquisition scheme to simultaneously determine metabolite-specific concentrations and transverse relaxation times within realistic clinical scan times. Partly truncated multi-TE data are acquired as an echo train in a single acquisition (multi-echo single-shot [MESS]). A 2D multiparametric model fitting approach combines truncated, low-resolved short TE data with fully sampled, highly resolved, longer TE data to yield concentration and T2 estimates for major brain metabolites simultaneously. Cramer-Rao lower bounds (CRLB) are used as a measure of performance. The novel scheme was compared with traditional multi-echo multi-shot methods. In silico, in vitro, and in vivo experiments support the findings. MESS schemes, requiring only 2 min 12 s for the acquisition of three echo times, provide valid concentration and relaxation estimates for multiple metabolites and outperform traditional methods for simultaneous determinations of metabolite-specific T2 s and concentrations, with improvements ranging from 5% to 30% for T2 s and from 10% to 50% for concentrations. However, substantial unsuppressed residual water signals may hamper the method's reproducibility, as observed in an initial experiment setup that prioritizes short TEs with severely truncated acquisition for the benefit of signal-to-noise ratio (SNR). Nevertheless, CRLB have been confirmed to be well suited as design criteria, and within-session repeatability approaches CRLB when residual water is removed in postprocessing by exploiting longer and less truncated data recordings. MESS MRS combined with 2D model fitting promises comparable accuracy, increased precision, or inversely shorter experimental times compared with traditional approaches. However, the optimal design must be investigated as a trade-off between SNR, the truncation factor, and TE batch selections, all of which influence the robustness of estimations.

Stratification of prostate cancer patients into low- and high-grade groups using multiparametric magnetic resonance radiomics with dynamic contrast-enhanced image joint histograms.

PURPOSE: This study aimed to investigate the potential of stratification of prostate cancer patients into low- and high-grade groups (GGs) using multiparametric magnetic resonance (mpMR) radiomics in conjunction with two-dimensional (2D) joint histograms computed with dynamic contrast-enhanced (DCE) images. METHODS: A total of 101 prostate cancer regions extracted from the MR images of 44 patients were identified and divided into training (n = 31 with 72 cancer regions) and test datasets (n = 13 with 29 cancer regions). Each dataset included low-grade tumors (International Society of Urological Pathology [ISUP] GG ≤ 2) and high-grade tumors (ISUP GG ≥ 3). A total of 137,970 features consisted of mpMR image (16 types of images in four sequences)-based and joint histogram (DCE images at 10 phases)-based features for each cancer region. Joint histogram features can visualize temporally changing perfusion patterns in prostate cancer based on the joint histograms between different phases or subtraction phases of DCE images. Nine signatures (a set of significant features related to GGs) were determined using the best combinations of features selected using the least absolute shrinkage and selection operator. Further, support vector machine models with the nine signatures were built based on a leave-one-out cross-validation for the training dataset and evaluated with receiver operating characteristic (ROC) curve analysis. RESULTS: The signature showing the best performance was constructed using six features derived from the joint histograms, DCE original images, and apparent diffusion coefficient maps. The areas under the ROC curves for the training and test datasets were 1.00 and 0.985, respectively. CONCLUSION: This study suggests that the proposed approach with mpMR radiomics in conjunction with 2D joint histogram computed with DCE images could have the potential to stratify prostate cancer patients into low- and high-GGs.

Detection of clinically significant prostate cancer with 18F-DCFPyL PET/multiparametric MR.

PURPOSE: To assess whether 18F-DCFPyL PET/multiparametric (mp)MR contributes to the diagnosis of clinically significant (cs) prostate cancer (PCa) compared to mpMR in patients with suspicion of PCa, or patients being considered for focal ablative therapies (FT). PATIENTS AND METHODS: This ethics review board-approved, prospective study included 55 men with suspicion of PCa and negative systematic biopsies or clinically discordant low-risk PCa (n = 21) or those being considered for FT (n = 34) who received 18F-DCFPyL PET/mpMR. Each modality, PET, mpMR, and PET/MR (using the PROMISE classification), was assessed independently. All suspicious lesions underwent PET/MR-ultrasound fusion biopsies. RESULTS: There were 45/55 patients (81.8%) that had histologically proven PCa and 41/55 (74.5%) were diagnosed with csPCa. Overall, 61/114 lesions (53.5%) identified on any modality were malignant; 49/61 lesions (80.3%) were csPCa. On lesion-level analysis, for detection of csPCa, the sensitivity of PET was higher than that of mpMR and PET/MR (86% vs 67% and 69% [p = 0.027 and 0.041, respectively]), but at a lower specificity (32% vs 85% and 86%, respectively [p < 0.001]). The performance of MR and PET/MR was comparable. For identification of csPCa in PI-RADS ≥ 3 lesions, the AUC (95% CI) for PET, mpMR, and PET/MR was 0.75 (0.65-0.86), 0.69 (0.56-0.82), and 0.78 (0.67-0.89), respectively. The AUC for PET/MR was significantly larger than that of mpMR (p = 0.04). CONCLUSION: PSMA PET detects more csPCa than mpMR, but at low specificity. The performance PET/MR is better than mpMR for detection of csPCa in PI-RADS ≥ 3 lesions. CLINICAL REGISTRATION: NCT03149861.

Noninvasive Prediction of IDH1 Mutation and ATRX Expression Loss in Low-Grade Gliomas Using Multiparametric MR Radiomic Features.

BACKGROUND: Noninvasive detection of isocitrate dehydrogenase 1 mutation (IDH1(+)) and loss of nuclear alpha thalassemia/mental retardation syndrome X-linked expression ((ATRX(-)) are clinically meaningful for molecular stratification of low-grade gliomas (LGGs). PURPOSE: To study a radiomic approach based on multiparametric MR for noninvasively determining molecular status of IDH1(+) and ATRX(-) in patients with LGG. STUDY TYPE: Retrospective, radiomics. POPULATION: Fifty-seven LGG patients with IDH1(+) (n = 36 with 19 ATRX(-) and 17 ATRX(+) patients) and IDH1(-) (n = 21). FIELD STRENGTH/SEQUENCE: 3.0T MRI / 3D arterial spin labeling (3D-ASL), T2 /fluid-attenuated inversion recovery (T2 FLAIR), and diffusion-weighted imaging (DWI). ASSESSMENT: In all, 265 high-throughput radiomic features were extracted on each tumor volume of interest from T2 FLAIR and the other three parametric maps of ASL-derived cerebral blood flow (CBF), DWI-derived apparent diffusion coefficient (ADC), and exponential ADC (eADC). Optimal feature subsets were selected as using the support vector machine with a recursive feature elimination algorithm (SVM-RFE). Receiver operating characteristic curve (ROC) analysis was employed to assess the efficiency for identifying the IDH1(+) and ATRX(-) status. STATISTICAL TESTS: Student's t-test, chi-square test, and Fisher's exact test were applied to confirm whether intergroup significant differences exist between molecular subtypes decided by IDH1 and ATRX. RESULTS: Optimal SVM predictive models of IDH1(+) and ATRX(-) were established using 28 features from T2 Flair, ADC, eADC, and CBF and six features from T2 Flair, ADC, and CBF. The accuracies/AUCs/sensitivity/specifity/PPV/NPV of predicting IDH1(+) in LGG were 94.74%/0.931/100%/85.71%/92.31%/100%, and those of predicting ATRX(-) in LGG with IDH1(+) were 91.67%/0.926/94.74%/88.24%/90.00%/93.75%, respectively. DATA CONCLUSION: Using the optimal texture features extracted from multiple MR sequences or parametric maps, a promising stratifying strategy was acquired for predicting molecular subtypes of IDH1 and ATRX in LGGs. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;49:808-817.

Imaging biomarkers for clinical applications in neuro-oncology: current status and future perspectives.

Biomarker discovery and development are popular for detecting the subtle diseases. However, biomarkers are needed to be validated and approved, and even fewer are ever used clinically. Imaging biomarkers have a crucial role in the treatment of cancer patients because they provide objective information on tumor biology, the tumor's habitat, and the tumor's signature in the environment. Tumor changes in response to an intervention complement molecular and genomic translational diagnosis as well as quantitative information. Neuro-oncology has become more prominent in diagnostics and targeted therapies. The classification of tumors has been actively updated, and drug discovery, and delivery in nanoimmunotherapies are advancing in the field of target therapy research. It is important that biomarkers and diagnostic implements be developed and used to assess the prognosis or late effects of long-term survivors. An improved realization of cancer biology has transformed its management with an increasing emphasis on a personalized approach in precision medicine. In the first part, we discuss the biomarker categories in relation to the courses of a disease and specific clinical contexts, including that patients and specimens should both directly reflect the target population and intended use. In the second part, we present the CT perfusion approach that provides quantitative and qualitative data that has been successfully applied to the clinical diagnosis, treatment and application. Furthermore, the novel and promising multiparametric MR imageing approach will provide deeper insights regarding the tumor microenvironment in the immune response. Additionally, we briefly remark new tactics based on MRI and PET for converging on imaging biomarkers combined with applications of bioinformatics in artificial intelligence. In the third part, we briefly address new approaches based on theranostics in precision medicine. These sophisticated techniques merge achievable standardizations into an applicatory apparatus for primarily a diagnostic implementation and tracking radioactive drugs to identify and to deliver therapies in an individualized medicine paradigm. In this article, we describe the critical principles for imaging biomarker characterization and discuss the current status of CT, MRI and PET in finiding imaging biomarkers of early disease.

A Prospective Study Assessing the Post-Prostatectomy Detection Rate of a Presumed Local Failure at mpMR with Either 64CuCl2 or 64CuPSMA PET/CT.

BACKGROUND: We aimed assess the detection rate (DR) of positron emission tomography/computed tomography with two novel tracers in patients referred for salvage radiotherapy (sRT) with a presumed local recurrence at multiparametric magnetic resonance (mpMR) after radical prostatectomy (RP). METHODS: The present prospective study was conducted at a single institution between August 2017 and June 2020. Eligibility criteria were undetectable PSA after RP; subsequent biochemical recurrence (two consecutive PSA rises to 0.2 ng/mL or greater); a presumed local failure at mpMR; no distant metastases at 18F-fluorocholine PET/CT (CH/PET); no previous history of androgen deprivation therapy. Patients were offered both 64CuCl2 PET/CT (CU/PET) and 64Cu-PSMA PET/CT (PSMA/PET) before sRT. After image co-registration, PET findings were compared to mpMR ones in terms of DR and independent predictors of DR investigated at logistic regression. RESULTS: A total of 62 patients with 72 nodules at mpMR were accrued. Compared to mpMR (DR = 100%, 95%CI: 94.9-100%), DRs were 47.2% (95%CI: 36.1-58.6%) and 54.4% (95%CI: 42.7-65.7%) for CU/PET and PSMA/PET, respectively (p < 0.001 for both). Both experimental PET/CT performed particularly poorly at PSA levels consistent with early sRT. CONCLUSIONS: The two novel radiotracers are inferior to mpMR in restaging the prostatic fossa for sRT planning purposes, particularly in the context of early salvage radiotherapy.

Volumetric and Voxel-Wise Analysis of Dominant Intraprostatic Lesions on Multiparametric MRI.

Introduction: Multiparametric MR imaging (mpMRI) has shown promising results in the diagnosis and localization of prostate cancer. Furthermore, mpMRI may play an important role in identifying the dominant intraprostatic lesion (DIL) for radiotherapy boost. We sought to investigate the level of correlation between dominant tumor foci contoured on various mpMRI sequences. Methods: mpMRI data from 90 patients with MR-guided biopsy-proven prostate cancer were obtained from the SPIE-AAPM-NCI Prostate MR Classification Challenge. Each case consisted of T2-weighted (T2W), apparent diffusion coefficient (ADC), and Ktrans images computed from dynamic contrast-enhanced sequences. All image sets were rigidly co-registered, and the dominant tumor foci were identified and contoured for each MRI sequence. Hausdorff distance (HD), mean distance to agreement (MDA), and Dice and Jaccard coefficients were calculated between the contours for each pair of MRI sequences (i.e., T2 vs. ADC, T2 vs. Ktrans, and ADC vs. Ktrans). The voxel wise spearman correlation was also obtained between these image pairs. Results: The DILs were located in the anterior fibromuscular stroma, central zone, peripheral zone, and transition zone in 35.2, 5.6, 32.4, and 25.4% of patients, respectively. Gleason grade groups 1-5 represented 29.6, 40.8, 15.5, and 14.1% of the study population, respectively (with group grades 4 and 5 analyzed together). The mean contour volumes for the T2W images, and the ADC and Ktrans maps were 2.14 ± 2.1, 2.22 ± 2.2, and 1.84 ± 1.5 mL, respectively. Ktrans values were indistinguishable between cancerous regions and the rest of prostatic regions for 19 patients. The Dice coefficient and Jaccard index were 0.74 ± 0.13, 0.60 ± 0.15 for T2W-ADC and 0.61 ± 0.16, 0.46 ± 0.16 for T2W-Ktrans. The voxel-based Spearman correlations were 0.20 ± 0.20 for T2W-ADC and 0.13 ± 0.25 for T2W-Ktrans. Conclusions: The DIL contoured on T2W images had a high level of agreement with those contoured on ADC maps, but there was little to no quantitative correlation of these results with tumor location and Gleason grade group. Technical hurdles are yet to be solved for precision radiotherapy to target the DILs based on physiological imaging. A Boolean sum volume (BSV) incorporating all available MR sequences may be reasonable in delineating the DIL boost volume.

Future Perspectives in Multiparametric Prostate MR Imaging.

Multiparametric MR imaging is being used for prostate cancer diagnosis. However, many cancers are missed and the performance needs to improve before it can be used for population-level screening. We can expect standardization of multiparametric MR imaging and increased use of quantitative multiparametric MR imaging, which will lead to more reproducible results and improved interpretation. The development and integration of new acquisition techniques and use of artificial intelligence for image interpretation can lead to implementation of new clinical MR methods. These will lead to increased adoption of multiparametric MR imaging for prostate cancer diagnosis and for guiding intervention and follow-up.

MR Imaging-Guided Focal Therapies of Prostate Cancer.

MR imaging-guided focal therapy is a viable treatment option for patients with localized prostate cancer. After the identification of a malignant focus in the prostate gland on multiparametric MR imaging, treatment can be directed in a precise fashion to the area of interest. The goal of focal therapy is to eradicate prostate cancer while minimizing complications that can affect quality of life. Currently, the most commonly used methods of focal treatment of prostate cancer are cryotherapy, high-intensity focused ultrasound, and laser ablation.

In vivo magnetic resonance imaging techniques for structural and functional characterization of murine model kidneys.

Murine models are used in a wide range of renal studies, from those assessing the role of molecular and genetic factors in mammalian development and congenital diseases, to developing and screening new therapeutics. In studies of these models, magnetic resonance imaging (MRI) techniques are playing an ever increasing role in characterizing both structural and functional changes of the kidneys. This chapter details the use of MRI for this purpose-from acquisition to image analysis. An overview of the wide range of characterization that can be performed by this technology is first given. Next, basic image analysis and more advanced image processing techniques are detailed. The utility of MR for characterizing anatomical and physiological properties of murine models of disease is supplemented with data from our work studying polycystic kidney disease.

Multiparametric MR imaging of the Prostate: Interpretation Including Prostate Imaging Reporting and Data System Version 2.

mp-MRI of the prostate is a complex study that combines anatomic and functional imaging. The complexity of this technique, along with an increasing demand, has brought new challenges to imaging interpretation. The Prostate Imaging Reporting and Data System provides radiologists with guidelines to standardize interpretation. This article discusses the interpretation of the pulse sequences recommended in the Prostate Imaging Reporting and Data System version 2 guidelines, reviews advanced quantitative imaging tools, and discusses future directions.

Multiparametric Prostate MR Imaging: Impact on Clinical Staging and Decision Making.

Meaningful changes to the approach of prostate cancer staging and management have been made over the past decade with increasing demand for high-quality multiparametric MR imaging (mpMRI) of the prostate. This article focuses on the evolving paradigm of prostate cancer staging, with emphasis on the role of mpMRI on staging and its integration into clinical decision making. Current prostate cancer staging systems are defined and mpMRI's role in the detection of non-organ-confined disease and how it has an impact on the selection of appropriate next steps are discussed. Several imaging pitfalls, limitations, and future directions of mpMRI also are discussed.

Multiparametric MR imaging of the Prostate: Interpretation Including Prostate Imaging Reporting and Data System Version 2.

mp-MRI of the prostate is a complex study that combines anatomic and functional imaging. The complexity of this technique, along with an increasing demand, has brought new challenges to imaging interpretation. The Prostate Imaging Reporting and Data System provides radiologists with guidelines to standardize interpretation. This article discusses the interpretation of the pulse sequences recommended in the Prostate Imaging Reporting and Data System version 2 guidelines, reviews advanced quantitative imaging tools, and discusses future directions.

Multiparametric Prostate MR Imaging: Impact on Clinical Staging and Decision Making.

Meaningful changes to the approach of prostate cancer staging and management have been made over the past decade with increasing demand for high-quality multiparametric MR imaging (mpMRI) of the prostate. This article focuses on the evolving paradigm of prostate cancer staging, with emphasis on the role of mpMRI on staging and its integration into clinical decision making. Current prostate cancer staging systems are defined and mpMRI's role in the detection of non-organ-confined disease and how it has an impact on the selection of appropriate next steps are discussed. Several imaging pitfalls, limitations, and future directions of mpMRI also are discussed.

Defining the optimal method for reporting prostate cancer grade and tumor extent on magnetic resonance/ultrasound fusion-targeted biopsies.

Magnetic resonance (MR)/ultrasound fusion-targeted biopsy (TB) routinely samples multiple cores from each MR lesion of interest. Pathologists can evaluate the extent of cancer involvement and grade using an individual core (IC) or aggregate (AG) method, which could potentially lead to differences in reporting. We reviewed patients who underwent TB followed by radical prostatectomy (RP). TB cores were evaluated for grade and tumor extent by 2 methods. In the IC method, the grade for each TB lesion was based on the core with the highest Gleason score. Tumor extent for each TB was based on the core with the highest percent of tumor involvement. In the AG method, the tumor from all cores within each TB lesion was aggregated to determine the final composite grade and percentage of tumor involvement. Each method was compared with MR lesional volume, MR lesional density (lesion volume/prostate volume), and RP. Fifty-five patients underwent TB followed by RP. Extent of tumor by the AG method showed a better correlation with target lesion volume (r= 0.27,P= .022) and lesional density (r = 0.32, P = .008) than did the IC method (r= 0.19 [P = .103] andr= 0.22 [P = .062]), respectively. Extent of tumor on TB was associated with extraprostatic extension on RP by the AG method (P= .04), but not by the IC method. This association was significantly higher in patients with a grade group (GG) of 3 or higher (P= .03). A change in cancer grade occurred in 3 patients when comparing methods (2 downgraded GG3 to GG2, 1 downgraded GG4 to GG3 by the AG method). For multiple cores obtained via TB, the AG method better correlates with target lesion volume, lesional density, and extraprostatic extension.

MR Imaging of Prostate Zonal Anatomy.

McNeal first described the zonal anatomy of the prostate about 40 years ago, outlining 4 zones of the prostate and defining their relation to the urethra and the ejaculatory ducts. The zonal anatomy remains the accepted model for describing the prostate and the zones are well-depicted on MR imaging, including the central zone, which until recently was grouped with the transition zone in the radiology literature. An accurate understanding of the zonal anatomy and periprostatic anatomy is key for accurate interpretation of the prostate MR imaging.

Detection of recurrent prostate cancer after radical prostatectomy: comparison of 11C-choline PET/CT with pelvic multiparametric MR imaging with endorectal coil.

UNLABELLED: The aim of this study was to compare (11)C-choline PET/CT with pelvic multiparametric MR imaging for detection of recurrent prostate carcinoma in patients with suspected recurrence after radical prostatectomy and to identify an optimal imaging method to restage these patients. METHODS: This was a retrospective, single-institution study of 115 prostatectomy patients with suspected tumor recurrence who underwent both (11)C-choline PET/CT and multiparametric MR imaging with endorectal coil. The reference standard included histopathology, treatment change, and imaging follow-up for determination of locally recurrent tumor, lymph node (LN) metastases, and skeletal metastases. Two nuclear medicine and 2 genitourinary radiologists independently and in a masked manner reviewed PET/CT and multiparametric MR imaging, respectively. The reviewers assessed for local recurrence in the prostatectomy bed as well as LN and bone metastases, rating their diagnostic confidence with a 5-point scoring system for each location. Receiver-operating-characteristic analysis was used to compare the 2 modalities. RESULTS: The standard of reference (either positive or negative) for the diagnosis of local recurrence and pelvic LN and bone metastases was met in 87, 70, and 95 patients, respectively. Documented local recurrence and pelvic LN and bone metastases was present in 61 of 87 (70.1%), 50 of 70 (71.4%), and 16 of 95 (16.8%) patients, respectively. Patient-based area under the receiver-operating-characteristic curves of multiparametric MR imaging versus PET/CT for the diagnosis of local recurrence and pelvic LN and bone metastases were 0.909 versus 0.761 (P = 0.0079), 0.812 versus 0.952 (P = 0.0064), and 0.927 versus 0.898 (P = 0.69), respectively. Among 61 patients with local recurrence, 32 patients (52.4%) were correctly diagnosed as having local recurrence by both multiparametric MR imaging and PET/CT, 22 (36.1%) were correctly diagnosed by multiparametric MR imaging only, 6 (9.8%) could not be diagnosed by either modality, and 1 (1.6%) was correctly diagnosed by PET/CT only. The patient-based sensitivity, specificity, and accuracy of multiparametric MR imaging for diagnosing local recurrence were 88.5% (54/61), 84.6% (22/26), and 87.4% (76/87) whereas those of PET/CT for detecting body LN or bone metastases were 92.3% (72/78), 100% (18/18), and 93.8% (90/96), respectively. CONCLUSION: Multiparametric MR imaging with endorectal coil is superior for the detection of local recurrence, PET/CT is superior for pelvic LN metastasis, and both were equally excellent for pelvic bone metastasis. (11)C-choline PET/CT and pelvic multiparametric MR imaging are complementary for restaging prostatectomy patients with suspected recurrent disease.

MR imaging of the prostate.

Multiparametric magnetic resonance (MR) imaging of the prostate is gaining acceptance in the management of prostate cancer. Emerging indications of prostate MR imaging may expand its use in the work-up of localized prostate cancer. Improvements in the standardization of prostate MR imaging techniques and reporting are needed for further establishment of the emerging roles of prostate MR imaging. This article describes the prostate MR imaging techniques and provides an approach for interpretation of prostate MR imaging studies. Established and emerging indications for prostate MR imaging are also reviewed.