Systematic evaluation of MRI-based characterization of tumor-associated vascular morphology and hemodynamics via a dynamic digital phantom.

Purpose: Validation of quantitative imaging biomarkers is a challenging task, due to the difficulty in measuring the ground truth of the target biological process. A digital phantom-based framework is established to systematically validate the quantitative characterization of tumor-associated vascular morphology and hemodynamics based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Approach: A digital phantom is employed to provide a ground-truth vascular system within which 45 synthetic tumors are simulated. Morphological analysis is performed on high-spatial resolution DCE-MRI data (spatial/temporal resolution = 30 to 300 µm/60 s) to determine the accuracy of locating the arterial inputs of tumor-associated vessels (TAVs). Hemodynamic analysis is then performed on the combination of high-spatial resolution and high-temporal resolution (spatial/temporal resolution = 60 to 300 µm/1 to 10 s) DCE-MRI data, determining the accuracy of estimating tumor-associated blood pressure, vascular extraction rate, interstitial pressure, and interstitial flow velocity. Results: The observed effects of acquisition settings demonstrate that, when optimizing the DCE-MRI protocol for the morphological analysis, increasing the spatial resolution is helpful but not necessary, as the location and arterial input of TAVs can be recovered with high accuracy even with the lowest investigated spatial resolution. When optimizing the DCE-MRI protocol for hemodynamic analysis, increasing the spatial resolution of the images used for vessel segmentation is essential, and the spatial and temporal resolutions of the images used for the kinetic parameter fitting require simultaneous optimization. Conclusion: An in silico validation framework was generated to systematically quantify the effects of image acquisition settings on the ability to accurately estimate tumor-associated characteristics.

Self-supervised multicontrast super-resolution for diffusion-weighted prostate MRI.

PURPOSE: This study addresses the challenge of low resolution and signal-to-noise ratio (SNR) in diffusion-weighted images (DWI), which are pivotal for cancer detection. Traditional methods increase SNR at high b-values through multiple acquisitions, but this results in diminished image resolution due to motion-induced variations. Our research aims to enhance spatial resolution by exploiting the global structure within multicontrast DWI scans and millimetric motion between acquisitions. METHODS: We introduce a novel approach employing a "Perturbation Network" to learn subvoxel-size motions between scans, trained jointly with an implicit neural representation (INR) network. INR encodes the DWI as a continuous volumetric function, treating voxel intensities of low-resolution acquisitions as discrete samples. By evaluating this function with a finer grid, our model predicts higher-resolution signal intensities for intermediate voxel locations. The Perturbation Network's motion-correction efficacy was validated through experiments on biological phantoms and in vivo prostate scans. RESULTS: Quantitative analyses revealed significantly higher structural similarity measures of super-resolution images to ground truth high-resolution images compared to high-order interpolation (p < $$ < $$ 0.005). In blind qualitative experiments, 96 . 1 % $$ 96.1\% $$ of super-resolution images were assessed to have superior diagnostic quality compared to interpolated images. CONCLUSION: High-resolution details in DWI can be obtained without the need for high-resolution training data. One notable advantage of the proposed method is that it does not require a super-resolution training set. This is important in clinical practice because the proposed method can easily be adapted to images with different scanner settings or body parts, whereas the supervised methods do not offer such an option.

Four-quadrant vector mapping of hybrid multidimensional MRI data for the diagnosis of prostate cancer.

PURPOSE: The interpretation of prostate multiparametric magnetic resonance imaging (MRI) is subjective in nature, and there is large inter-observer variability among radiologists and up to 30% of clinically significant cancers are missed. This has motivated the development of new MRI techniques and sequences, especially quantitative approaches to improve prostate cancer diagnosis. Using hybrid multidimensional MRI, apparent diffusion coefficient (ADC) and T2 have been shown to change as a function of echo time (TE) and b-values, and that this dependence is different for cancer and benign tissue, which can be exploited for prostate cancer diagnosis. The purpose of this study is to investigate whether four-quadrant vector mapping of hybrid multidimensional MRI (HM-MRI) data can be used to diagnose prostate cancer (PCa) and determine cancer aggressiveness. METHODS: Twenty-one patients with confirmed PCa underwent preoperative MRI prior to radical prostatectomy. Axial HM-MRI were acquired with all combinations of TE = 47, 75, 100 ms and b-values of 0, 750, 1500 s/mm2 , resulting in a 3 × 3 data matrix associated with each voxel. Prostate Quadrant (PQ) mapping analysis represents HM-MRI data for each voxel as a color-coded vector in the four-quadrant space of HM-MRI parameters (a 2D matrix of signal values for each combination of b-value and TE) with associated amplitude and angle information representing the change in T2 and ADC as a function of b-value and TE, respectively. RESULTS: Cancers have a higher PQ4 (22.50% ± 21.27%) and lower PQ2 (69.86% ± 28.24%) compared to benign tissue: peripheral, transition, and central zone (PQ4 = 0.13% ± 0.56%, 5.73% ± 15.07%, 2.66% ± 4.05%, and PQ2 = 98.51% ± 3.05%, 86.18% ± 21.75%, 93.38% ± 9.88%, respectively). Cancers have a higher vector angle (206.5 ± 41.8°) and amplitude (0.017 ± 0.013) compared to benign tissue. PQ metrics showed moderate correlation with Gleason score (|ρ| = 0.388-0.609), with more aggressive cancers being associated with increased PQ4 and angle and reduced PQ2 and amplitude. A combination of four-quadrant analysis metrics provided an area under the curve of 0.904 (p < 0.001) for the differentiation of prostate cancer from benign prostatic tissue. CONCLUSIONS: Four-quadrant vector mapping of HM-MRI data provides effective cancer markers, with cancers associated with high PQ4 and high vector angle and lower PQ2 and vector amplitude.

External Evaluation of a Mammography-based Deep Learning Model for Predicting Breast Cancer in an Ethnically Diverse Population.

Purpose: To externally evaluate a mammography-based deep learning (DL) model (Mirai) in a high-risk racially diverse population and compare its performance with other mammographic measures. Materials and Methods: A total of 6435 screening mammograms in 2096 female patients (median age, 56.4 years ± 11.2 [SD]) enrolled in a hospital-based case-control study from 2006 to 2020 were retrospectively evaluated. Pathologically confirmed breast cancer was the primary outcome. Mirai scores were the primary predictors. Breast density and Breast Imaging Reporting and Data System (BI-RADS) assessment categories were comparative predictors. Performance was evaluated using area under the receiver operating characteristic curve (AUC) and concordance index analyses. Results: Mirai achieved 1- and 5-year AUCs of 0.71 (95% CI: 0.68, 0.74) and 0.65 (95% CI: 0.64, 0.67), respectively. One-year AUCs for nondense versus dense breasts were 0.72 versus 0.58 (P = .10). There was no evidence of a difference in near-term discrimination performance between BI-RADS and Mirai (1-year AUC, 0.73 vs 0.68; P = .34). For longer-term prediction (2-5 years), Mirai outperformed BI-RADS assessment (5-year AUC, 0.63 vs 0.54; P < .001). Using only images of the unaffected breast reduced the discriminatory performance of the DL model (P < .001 at all time points), suggesting that its predictions are likely dependent on the detection of ipsilateral premalignant patterns. Conclusion: A mammography DL model showed good performance in a high-risk external dataset enriched for African American patients, benign breast disease, and BRCA mutation carriers, and study findings suggest that the model performance is likely driven by the detection of precancerous changes.Keywords: Breast, Cancer, Computer Applications, Convolutional Neural Network, Deep Learning Algorithms, Informatics, Epidemiology, Machine Learning, Mammography, Oncology, Radiomics Supplemental material is available for this article. © RSNA, 2023See also commentary by Kontos and Kalpathy-Cramer in this issue.

Prostate Cancers Invisible on Multiparametric MRI: Pathologic Features in Correlation with Whole-Mount Prostatectomy.

We investigated why some prostate cancers (PCas) are not identified on multiparametric MRI (mpMRI) by using ground truth reference from whole-mount prostatectomy specimens. A total of 61 patients with biopsy-confirmed PCa underwent 3T mpMRI followed by prostatectomy. Lesions visible on MRI prospectively or retrospectively identified after correlating with histology were considered "identified cancers" (ICs). Lesions that could not be identified on mpMRI were considered "unidentified cancers" (UCs). Pathologists marked the Gleason score, stage, size, and density of the cancer glands and performed quantitative histology to calculate the tissue composition. Out of 115 cancers, 19 were unidentified on MRI. The UCs were significantly smaller and had lower Gleason scores and clinical stage lesions compared with the ICs. The UCs had significantly (p < 0.05) higher ADC (1.34 ± 0.38 vs. 1.02 ± 0.30 µm2/ms) and T2 (117.0 ± 31.1 vs. 97.1 ± 25.1 ms) compared with the ICs. The density of the cancer glands was significantly (p = 0.04) lower in the UCs. The percentage of the Gleason 4 component in Gleason 3 + 4 lesions was nominally (p = 0.15) higher in the ICs (20 ± 12%) compared with the UCs (15 ± 8%). The UCs had a significantly lower epithelium (32.9 ± 21.5 vs. 47.6 ± 13.1%, p = 0.034) and higher lumen volume (20.4 ± 10.0 vs. 13.3 ± 4.1%, p = 0.021) compared with the ICs. Independent from size and Gleason score, the tissue composition differences, specifically, the higher lumen and lower epithelium in UCs, can explain why some of the prostate cancers cannot be identified on mpMRI.

Multi-model sequential analysis of MRI data for microstructure prediction in heterogeneous tissue.

We propose a general method for combining multiple models to predict tissue microstructure, with an exemplar using in vivo diffusion-relaxation MRI data. The proposed method obviates the need to select a single 'optimum' structure model for data analysis in heterogeneous tissues where the best model varies according to local environment. We break signal interpretation into a three-stage sequence: (1) application of multiple semi-phenomenological models to predict the physical properties of tissue water pools contributing to the observed signal; (2) from each Stage-1 semi-phenomenological model, application of a tissue microstructure model to predict the relative volumes of tissue structure components that make up each water pool; and (3) aggregation of the predictions of tissue structure, with weightings based on model likelihood and fractional volumes of the water pools from Stage-1. The multiple model approach is expected to reduce prediction variance in tissue regions where a complex model is overparameterised, and bias where a model is underparameterised. The separation of signal characterisation (Stage-1) from biological assignment (Stage-2) enables alternative biological interpretations of the observed physical properties of the system, by application of different tissue structure models. The proposed method is exemplified with human prostate diffusion-relaxation MRI data, but has potential application to a wide range of analyses where a single model may not be optimal throughout the sampled domain.

Bilateral asymmetry of quantitative parenchymal kinetics at ultrafast DCE-MRI predict response to neoadjuvant chemotherapy in patients with HER2+ breast cancer.

PURPOSE: To assess whether measurement of the bilateral asymmetry of semiquantitative and quantitative perfusion parameters from ultrafast dynamic contrast-enhanced MRI (DCE-MRI), allows early prediction of pathologic response after neoadjuvant chemotherapy (NAC) in patients with HER2+ breast cancer. MATERIALS AND METHODS: Twenty-eight female patients with HER2+ breast cancer treated with NAC who underwent pre-NAC ultrafast DCE-MRI (3-9 s/phase) were enrolled for this study. Four semiquantitative and two quantitative parenchymal parameters were calculated for each patient. Ipsilateral/contralateral (I/C) ratio (for four parameters) and the difference between (for two parameters) ipsi- and contra-lateral parenchymal kinetic parameters (kBPE) were compared for patients with pathologic complete response (pCR) and those having residual disease. Lasso regression with leave-one-out cross validation was used to determine the optimal combination of parameters for a regression model and multivariable logistic regression was used to identify independent predictors for pCR. Chi-squared test, two-sided t-test and Kruskal-Wallis test were used. RESULTS: The Ktrans I/C ratio cutoff value of 1.11 had a sensitivity of 83.3% and specificity of 75% for pCR. The ve I/C ratio cutoff value of 1.1 had a sensitivity of 75% and specificity of 81.3% for pCR. The area under the receiver operating characteristic curve of the three-kBPE parameter model, including initial area under the enhancement curve (AUC30) I/C ratio, KtransI/C ratio and ve I/C ratio, was 0.89 with sensitivity of 91.7% at specificity of 81.3%. CONCLUSION: Quantitative assessment of bilateral asymmetry kBPE from pre-NAC ultrafast DCE-MRI can predict pCR in patients with HER2+ breast cancer.

Parametric maps of spatial two-tissue compartment model for prostate dynamic contrast enhanced MRI - comparison with the standard tofts model in the diagnosis of prostate cancer.

The spatial two-tissue compartment model (2TCM) was used to analyze prostate dynamic contrast enhanced (DCE) MRI data and compared with the standard Tofts model. A total of 29 patients with biopsy-confirmed prostate cancer were included in this IRB-approved study. MRI data were acquired on a Philips Achieva 3T-TX scanner. After T2-weighted and diffusion-weighted imaging, DCE data using 3D T1-FFE mDIXON sequence were acquired pre- and post-contrast media injection (0.1 mmol/kg Multihance) for 60 dynamic scans with temporal resolution of 8.3 s/image. The 2TCM has one fast ([Formula: see text] and [Formula: see text]) and one slow ([Formula: see text] and [Formula: see text]) exchanging compartment, compared with the standard Tofts model parameters (Ktrans and kep). On average, prostate cancer had significantly higher values (p < 0.01) than normal prostate tissue for all calculated parameters. There was a strong correlation (r = 0.94, p < 0.001) between Ktrans and [Formula: see text] for cancer, but weak correlation (r = 0.28, p < 0.05) between kep and [Formula: see text]. Average root-mean-square error (RMSE) in fits from the 2TCM was significantly smaller (p < 0.001) than the RMSE in fits from the Tofts model. Receiver operating characteristic (ROC) analysis showed that fast [Formula: see text] had the highest area under the curve (AUC) than any other individual parameter. The combined four parameters from the 2TCM had a considerably higher AUC value than the combined two parameters from the Tofts model. The 2TCM is useful for quantitative analysis of prostate DCE-MRI data and provides new information in the diagnosis of prostate cancer.

Pharmacokinetic Analysis of Enhancement-Constrained Acceleration (ECA) reconstruction-based high temporal resolution breast DCE-MRI.

The high spatial and temporal resolution of dynamic contrast-enhanced MRI (DCE-MRI) can improve the diagnostic accuracy of breast cancer screening in patients who have dense breasts or are at high risk of breast cancer. However, the spatiotemporal resolution of DCE-MRI is limited by technical issues in clinical practice. Our earlier work demonstrated the use of image reconstruction with enhancement-constrained acceleration (ECA) to increase temporal resolution. ECA exploits the correlation in k-space between successive image acquisitions. Because of this correlation, and due to the very sparse enhancement at early times after contrast media injection, we can reconstruct images from highly under-sampled k-space data. Our previous results showed that ECA reconstruction at 0.25 seconds per image (4 Hz) can estimate bolus arrival time (BAT) and initial enhancement slope (iSlope) more accurately than a standard inverse fast Fourier transform (IFFT) when k-space data is sampled following a Cartesian based sampling trajectory with adequate signal-to-noise ratio (SNR). In this follow-up study, we investigated the effect of different Cartesian based sampling trajectories, SNRs and acceleration rates on the performance of ECA reconstruction in estimating contrast media kinetics in lesions (BAT, iSlope and Ktrans) and in arteries (Peak signal intensity of first pass, time to peak, and BAT). We further validated ECA reconstruction with a flow phantom experiment. Our results show that ECA reconstruction of k-space data acquired with 'Under-sampling with Repeated Advancing Phase' (UnWRAP) trajectories with an acceleration factor of 14, and temporal resolution of 0.5 s/image and high SNR (SNR ≥ 30 dB, noise standard deviation (std) < 3%) ensures minor errors (5% or 1 s error) in lesion kinetics. Medium SNR (SNR ≥ 20 dB, noise std ≤ 10%) was needed to accurately measure arterial enhancement kinetics. Our results also suggest that accelerated temporal resolution with ECA with 0.5 s/image is practical.

Improving reader accuracy and specificity with the addition of hybrid multidimensional-MRI to multiparametric-MRI in diagnosing clinically significant prostate cancers.

PURPOSE: Compare reader performance when adding the Hybrid Multidimensional-MRI (HM-MRI) map to multiparametric MRI (mpMRI+HM-MRI) versus mpMRI alone and inter-reader agreement in diagnosing clinically significant prostate cancers (CSPCa). METHODS: All 61 patients who underwent mpMRI (T2-, diffusion-weighted (DWI), and contrast-enhanced scans) and HM-MRI (with multiple TE/b-value combinations) before prostatectomy or MRI-fused-transrectal ultrasound-guided biopsy between August, 2012 and February, 2020, were retrospectively analyzed. Two experienced readers (R1, R2) and two less-experienced readers (less than 6-year MRI prostate experience) (R3, R4) interpreted mpMRI without/with HM-MRI in the same sitting. Readers recorded the PI-RADS 3-5 score, lesion location, and change in score after adding HM-MRI. Each radiologist's mpMRI+HM-MRI and mpMRI performance measures (AUC, sensitivity, specificity, PPV, NPV, and accuracy) based on pathology, and Fleiss' kappa inter-reader agreement was calculated and compared. RESULTS: Per-sextant R3 and R4 mpMRI+HM-MRI accuracy (82% 81% vs. 77%, 71%; p=.006, <.001) and specificity (89%, 88% vs. 84%, 75%; p=.009, <.001) were higher than with mpMRI. Per-patient R4 mpMRI+HM-MRI specificity improved (48% from 7%; p<.001). R1 and R2 mpMRI+HM-MRI specificity per-sextant (80%, 93% vs. 81%, 93%; p=.51,>.99) and per-patient (37%, 41% vs. 48%, 37%; p=.16, .57) remained similar to mpMRI. R1 and R2 per-patient AUC with mpMRI+HM-MRI (0.63, 0.64 vs. 0.67, 0.61; p=.33, .36) remained similar to mpMRI, but R3 and R4 mpMRI+HM-MRI AUC (0.73, 0.62) approached R1 and R2 AUC. Per-patient inter-reader agreement, mpMRI+HM-MRI Fleiss Kappa, was higher than mpMRI (0.36 [95% CI 0.26, 0.46] vs. 0.17 [95% CI 0.07, 0.27]); p=.009). CONCLUSION: Adding HM-MRI to mpMRI (mpMRI+HM-MRI) improved specificity and accuracy for less-experienced readers, improving overall inter-reader agreement.

An Interactive App with Multi-parametric MRI - Whole-Mount Histology Correlation for Enhanced Prostate MRI Training of Radiology Residents.

RATIONALE AND OBJECTIVES: To validate the educational value of a newly created learning application in enhancing prostate MRI training of radiologists for detecting prostate cancer using an observer study. MATERIALS AND METHODS: An interactive learning app, LearnRadiology, was developed using a web-based framework to display multi-parametric prostate MRI images with whole-mount histology for 20 cases curated for unique pathology and teaching points. Twenty new prostate MRI cases, different from the ones used in the web app, were uploaded on 3D Slicer. Three radiologists (R1: radiologist; R2, R3: residents) blinded to pathology results were asked to mark areas suspected of cancer and provide a confidence score (1-5, with 5 being high confidence level). Then after a minimum memory washout period of 1 month, the same radiologists used the learning app and then repeated the same observer study. The diagnostic performance for detecting cancers before and after accessing the learning app was measured by correlating MRI with whole-mount pathology by an independent reviewer. RESULTS: The 20 subjects included in the observer study had 39 cancer lesions (13 Gleason 3 + 3, 17 Gleason 3 + 4, 7 Gleason 4 + 3, and 2 Gleason 4 + 5 lesions). The sensitivity (R1: 54% â†’ 64%, P = 0.08; R2: 44% â†’ 59%, P = 0.03; R3: 62% â†’ 72%, P = 0.04) and positive predictive value (R1: 68% â†’ 76%, P = 0.23; R2: 52% â†’ 79%, P = 0.01; R3: 48% â†’ 65%, P = 0.04) for all 3 radiologists improved after using the teaching app. The confidence score for true positive cancer lesion also improved significantly (R1: 4.0 ± 1.0 â†’ 4.3 ± 0.8; R2: 3.1 ± 0.8 â†’ 4.0 ± 1.1; R3: 2.8 ± 1.2 â†’ 4.1 ± 1.1; P < 0.05). CONCLUSION: The web-based and interactive LearnRadiology app learning resource can support medical student and postgraduate education by improving diagnostic performance of trainees for detecting prostate cancer.

Standardization of Breast Dynamic Contrast-enhanced MRI Signal with Application to the Assessment of Background Parenchymal Enhancement Rate.

BACKGROUND: There is currently no clinically accepted method for quantifying background parenchymal enhancement (BPE), though a sensitive method might allow individualized risk management based on the response to cancer-preventative hormonal therapy. OBJECTIVE: The objective of this pilot study is to demonstrate the utility of linear modeling of standardized dynamic contrast-enhanced MRI (DCEMRI) signal for quantifying changes in BPE rates. METHODS: On a retrospective database search, 14 women with DCEMRI examinations pre- and post- treatment with tamoxifen were identified. DCEMRI signal was averaged over the parenchymal ROIs to obtain time-dependent signal curves S(t). The gradient echo signal equation was used to standardize scale S(t) to values of (FA) ̃ = 10° and (TR) ̃ = 5.5 ms, and obtain the standardized parameters of DCE-MRI signal S ̃_p (t). Relative signal enhancement (〖RSE〗_p ) ̃ was calculated from S ̃_p, and the reference tissue method for T1 calculation was used to standardize (〖RSE〗_p ) ̃ to gadodiamide as the contrast agent, obtaining (RSE) ̃. (RSE) ̃, in the first 6 minutes, post-contrast administration was fit to a linear model with the slope α ̃_RSE denoting the standardized rate relative BPE. RESULTS: Changes in α ̃_RSE were not found to be significantly correlated with the average duration of tamoxifen treatment, age at the initiation of preventative treatment, or pre-treatment BIRADS breast density category. The average change in α ̃_RSE showed a large effect size of -1.12, significantly higher than -0.86 observed without signal standardization (p < 0.01). CONCLUSION: Linear modeling of BPE in standardized DCEMRI can provide quantitative measurements of BPE rates, improving sensitivity to changes due to tamoxifen treatment.

Characterization of Effects of Compressed Sensing on High Spectral and Spatial Resolution (HiSS) MRI with Comparison to SENSE.

High Spectral and Spatial resolution (HiSS) MRI shows high diagnostic performance in the breast. Acceleration methods based on k-space undersampling could allow stronger T2*-based image contrast and/or higher spectral resolution, potentially increasing diagnostic performance. An agar/oil phantom was prepared with water-fat boundaries perpendicular to the readout and phase encoding directions in a breast coil. HiSS MRI was acquired at 3T, at sensitivity encoding (SENSE) acceleration factors R of up to 10, and the R = 1 dataset was used to simulate corresponding compressed sensing (CS) accelerations. Image quality was evaluated by quantifying noise and artifact levels. Effective spatial resolution was determined via modulation transfer function analysis. Dispersion vs. absorption (DISPA) analysis and full width at half maximum (FWHM) quantified spectral lineshape changes. Noise levels remained constant with R for CS but amplified with SENSE. SENSE preserved the spatial resolution of HiSS MRI, while CS reduced it in the phase encoding direction. SENSE showed no effect on FWHM or DISPA markers, while CS increased FWHM. Thus, CS might perform better in noise-limited or geometrically constrained applications, but in geometric configurations specific to breast MRI, spectral analysis might be compromised, decreasing the diagnostic performance of HiSS MRI.

Comparison of synthesized and acquired high b -value diffusion-weighted MRI for detection of prostate cancer.

Background: High b -value diffusion-weighted images (DWI) are used for detection of clinically significant prostate cancer (csPCa). To decrease scan time and improve signal-to-noise ratio, high b -value (>1000 s/mm 2 ) images are often synthesized instead of acquired. Purpose: Qualitatively and quantitatively compare synthesized DWI (sDWI) to acquired (aDWI) for detection of csPCa. Study Type: Retrospective. Subjects: 151 consecutive patients who underwent prostate MRI and biopsy. Sequence: Axial DWI with b =0, 500, 1000, and 2000 s/mm 2 using a 3T clinical scanner using a 32-channel phased-array body coil. Assessment: We synthesized DWI for b =2000 s/mm 2 via extrapolation based on monoexponential decay, using b =0 and b =500 s/mm 2 (sDWI 500 ) and b =0, b =500, and b =1000 s/mm 2 (sDWI 1000 ). Differences between sDWI and aDWI were evaluated within regions of interest (ROIs). The maximum DWI value within each ROI was evaluated for prediction of csPCa. Classification accuracy was also compared to Restriction Spectrum Imaging restriction score (RSIrs), a previously validated biomarker based on multi-exponential DWI. Statistical Tests: Discrimination of csPCa was evaluated via area under the receiver operating characteristic curve (AUC). Statistical significance was assessed using bootstrap difference (two-sided α=0.05). Results: Within the prostate, mean ± standard deviation of percent mean differences between sDWI and aDWI signal were -46±35% for sDWI 1000 and -67±24% for sDWI 500 . AUC for aDWI, sDWI 500, sDWI 1000 , and RSIrs within the prostate 0.62[95% confidence interval: 0.53, 0.71], 0.63[0.54, 0.72], 0.65[0.56, 0.73] and 0.78[0.71, 0.86], respectively. When considering the whole field of view, classification accuracy and qualitative image quality decreased notably for sDWI compared to aDWI and RSIrs. Data Conclusion: sDWI is qualitatively comparable to aDWI within the prostate. However, hyperintense artifacts are introduced with sDWI in the surrounding pelvic tissue that interfere with quantitative cancer detection and might mask metastases. In the prostate, RSIrs yields superior quantitative csPCa detection than sDWI or aDWI.

Parametric maps of spatial two-tissue compartment model for prostate dynamic contrast enhanced MRI - comparison with the standard Tofts model in the diagnosis of prostate cancer.

The spatial two-tissue compartment model (2TCM) was used to analyze prostate dynamic contrast enhanced (DCE) MRI data and compared with the standard Tofts model. A total of 29 patients with biopsy-confirmed prostate cancer were included in this IRB-approved study. MRI data were acquired on a Philips Achieva 3T-TX scanner. After T2-weighted and diffusion-weighted imaging, DCE data using 3D T1-FFE mDIXON sequence were acquired pre- and post-contrast media injection (0.1 mmol/kg Multihance) for 60 dynamic scans with temporal resolution of 8.3 s/image. The 2TCM has one fast (K 1 trans and k 1 ep ) and one slow (K 2 trans and k 2 ep ) exchanging compartment, compared with the standard Tofts model parameters (K trans and k ep ). On average, prostate cancer had significantly higher values (p < 0.007) than normal prostate tissue for all calculated parameters. There was a strong correlation (r = 0.94, p < 0.0001) between K trans and K 1 trans for cancer, but weak correlation (r = 0.28, p < 0.05) between k ep and k 1 ep . Average root-mean-square error (RMSE) in fits from the 2TCM was significantly smaller (p < 0.001) than the RMSE in fits from the Tofts model. Receiver operating characteristic (ROC) analysis showed that fast K 1 trans had the highest area under the curve (AUC) than any other individual parameter. The combined four parameters from the 2TCM had a considerably higher AUC value than the combined two parameters from the Tofts model. The 2TCM may be useful for quantitative analysis of prostate DCE-MRI data and may provide new information in the diagnosis of prostate cancer.

Safely reducing unnecessary benign breast biopsies by applying non-mass and DWI directional variance filters to ADC thresholding.

BACKGROUND: Thresholding apparent diffusion coefficient (ADC) maps obtained from Diffusion-Weighted-Imaging (DWI) has been proposed for identifying benign lesions that can safely avoid biopsy. The presence of malignancies with high ADC values leads to high thresholds, limiting numbers of avoidable biopsies. PURPOSE: We evaluate two previously reported methods for identifying avoidable biopsies: using case-set dependent ADC thresholds that assure 100% sensitivity and using negative likelihood ratio (LR-) with a fixed ADC threshold of 1.50 × 10-3 mm2/s. We evaluated improvements in efficacy obtained by excluding non-mass lesions and lesions with anisotropic intra-lesion morphologic characteristics. STUDY TYPE: Prospective. POPULATION: 55 adult females with dense breasts with 69 BI-RADS 4 or 5 lesions (38 malignant, 31 benign) identified on ultrasound and mammography and imaged with MRI prior to biopsy. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T. DWI. ASSESSMENT: Analysis of DWI, including directional images was done on an ROI basis. ROIs were drawn on DWI images acquired prior to biopsy, referencing all available images including DCE, and mean ADC was measured. Anisotropy was quantified via variation in ADC values in the lesion core across directional DWI images. STATISTICAL TESTS: Improvement in specificity at 100% sensitivity was evaluated with exact McNemar test with 1-sided p-value < 0.05 indicating statistical significance. RESULTS: Using ADC thresholding that assures 100% sensitivity, non-mass and directional variance filtering improved the percent of avoidable biopsies to 42% from baseline of 10% achieved with ADC thresholding alone. Using LR-, filtering improved outcome to 0.06 from baseline 0.25 with ADC thresholding alone. ADC thresholding showed a lower percentage of avoidable biopsies in our cohort than reported in prior studies. When ADC thresholding was supplemented with filtering, the percentage of avoidable biopsies exceeded those of prior studies. DATA CONCLUSION: Supplementing ADC thresholding with filters excluding non-mass lesions and lesions with anisotropic characteristics on DWI can result in an increased number of avoidable biopsies.

The optimal 18F-fluoromisonidazole PET threshold to define tumor hypoxia in preclinical squamous cell carcinomas using pO2 electron paramagnetic resonance imaging as reference truth.

PURPOSE: To identify the optimal threshold in 18F-fluoromisonidazole (FMISO) PET images to accurately locate tumor hypoxia by using electron paramagnetic resonance imaging (pO2 EPRI) as ground truth for hypoxia, defined by pO2 [Formula: see text] 10 mmHg. METHODS: Tumor hypoxia images in mouse models of SCCVII squamous cell carcinoma (n = 16) were acquired in a hybrid PET/EPRI imaging system 2 h post-injection of FMISO. T2-weighted MRI was used to delineate tumor and muscle tissue. Dynamic contrast enhanced (DCE) MRI parametric images of Ktrans and ve were generated to model tumor vascular properties. Images from PET/EPR/MRI were co-registered and resampled to isotropic 0.5 mm voxel resolution for analysis. PET images were converted to standardized uptake value (SUV) and tumor-to-muscle ratio (TMR) units. FMISO uptake thresholds were evaluated using receiver operating characteristic (ROC) curve analysis to find the optimal FMISO threshold and unit with maximum overall hypoxia similarity (OHS) with pO2 EPRI, where OHS = 1 shows perfect overlap and OHS = 0 shows no overlap. The means of dice similarity coefficient, normalized Hausdorff distance, and accuracy were used to define the OHS. Monotonic relationships between EPRI/PET/DCE-MRI were evaluated with the Spearman correlation coefficient ([Formula: see text]) to quantify association of vasculature on hypoxia imaged with both FMISO PET and pO2 EPRI. RESULTS: FMISO PET thresholds to define hypoxia with maximum OHS (both OHS = 0.728 [Formula: see text] 0.2) were SUV [Formula: see text] 1.4 [Formula: see text] SUVmean and SUV [Formula: see text] 0.6 [Formula: see text] SUVmax. Weak-to-moderate correlations (|[Formula: see text]|< 0.70) were observed between PET/EPRI hypoxia images with vascular permeability (Ktrans) or fractional extracellular-extravascular space (ve) from DCE-MRI. CONCLUSION: This is the first in vivo comparison of FMISO uptake with pO2 EPRI to identify the optimal FMISO threshold to define tumor hypoxia, which may successfully direct hypoxic tumor boosts in patients, thereby enhancing tumor control.

Directional and inter-acquisition variability in diffusion-weighted imaging and editing for restricted diffusion.

PURPOSE: To evaluate and quantify inter-directional and inter-acquisition variation in diffusion-weighted imaging (DWI) and emphasize signals that report restricted diffusion to enhance cancer conspicuity, while reducing the effects of local microscopic motion and magnetic field fluctuations. METHODS: Ten patients with biopsy-proven prostate cancer were studied under an Institutional Review Board-approved protocol. Individual acquisitions of DWI signal intensities were reconstructed to calculate inter-acquisition distributions and their statistics, which were compared for healthy versus cancer tissue. A method was proposed to detect and filter the acquisitions affected by motion-induced signal loss. First, signals that reflect restricted diffusion were separated from the acquisitions that suffer from signal loss, likely due to microscopic motion, by imposing a cutoff value. Furthermore, corrected apparent diffusion coefficient maps were calculated by employing a weighted sum of the multiple acquisitions, instead of conventional averaging. These weights were calculated by applying a soft-max function to the set of acquisitions per-voxel, making the analysis immune to acquisitions with significant signal loss, even if the number of such acquisitions is high. RESULTS: Inter-acquisition variation is much larger than the Rician noise variance, local spatial variations, and the estimates of diffusion anisotropy based on the current data, as well as the published values of anisotropy. The proposed method increases the contrast for cancers and yields a sensitivity of 98 . 8 % $$ 98.8\% $$ with a false positive rate of 3 . 9 % $$ 3.9\% $$ . CONCLUSION: Motion-induced signal loss makes conventional signal-averaging suboptimal and can obscure signals from areas with restricted diffusion. Filtering or weighting individual acquisitions prior to image analysis can overcome this problem.

Comparing Radiologist Performance in Diagnosing Clinically Significant Prostate Cancer with Multiparametric versus Hybrid Multidimensional MRI.

Background Variability of acquisition and interpretation of prostate multiparametric MRI (mpMRI) persists despite implementation of the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1 due to the range of reader experience and subjectivity of lesion characterization. A quantitative method, hybrid multidimensional MRI (HM-MRI), may introduce objectivity. Purpose To compare performance, interobserver agreement, and interpretation time of radiologists using mpMRI versus HM-MRI to diagnose clinically significant prostate cancer. Materials and Methods In this retrospective analysis, men with prostatectomy or MRI-fused transrectal US biopsy-confirmed prostate cancer underwent mpMRI (triplanar T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging) and HM-MRI (with multiple echo times and b value combinations) from August 2012 to February 2020. Four readers with 1-20 years of experience interpreted mpMRI and HM-MRI examinations independently, with a 4-week washout period between interpretations. PI-RADS score, lesion location, and interpretation time were recorded. mpMRI and HM-MRI interpretation time, interobserver agreement (Cronbach alpha), and performance of area under the receiver operating characteristic curve (AUC) analysis were compared for each radiologist with use of bootstrap analysis. Results Sixty-one men (mean age, 61 years ± 8 [SD]) were evaluated. Per-patient AUC was higher for HM-MRI for reader 4 compared with mpMRI (AUCs for readers 1-4: 0.61, 0.71, 0.59, and 0.64 vs 0.66, 0.60, 0.50, and 0.46; P = .57, .20, .32, and .04, respectively). Per-patient specificity was higher for HM-MRI for readers 2-4 compared with mpMRI (specificity for readers 1-4: 48%, 78%, 48%, and 46% vs 37%, 26%, 0%, and 7%; P = .34, P < .001, P < .001, and P < .001, respectively). Diagnostic performance improved for the reader least experienced with HM-MRI, reader 4 (AUC, 0.64 vs 0.46; P = .04). HM-MRI interobserver agreement (Cronbach alpha = 0.88 [95% CI: 0.82, 0.92]) was higher than that of mpMRI (Cronbach alpha = 0.26 [95% CI: 0.10, 0.52]; α > .60 indicates reliability; P = .03). HM-MRI mean interpretation time (73 seconds ± 43 [SD]) was shorter than that of mpMRI (254 seconds ± 133; P = .03). Conclusion Radiologists had similar or improved diagnostic performance, higher interobserver agreement, and lower interpretation time for clinically significant prostate cancer with hybrid multidimensional MRI than multiparametric MRI. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Turkbey in this issue.

Physically implausible signals as a quantitative quality assessment metric in prostate diffusion-weighted MR imaging.

PURPOSE: To provide a quantitative assessment of diffusion-weighted MR images of the prostate through identification of PIDS which clearly represents artifacts in the data. We calculated the percentage and distribution of PIDS in prostate DWI and compare the amount of PIDS between mpMRI images obtained with and without an endorectal coil. METHODS: This IRB approved retrospective study (from 03/03/2014 to 03/10/2020), included 40 patients scanned with endorectal coil (ERC) and 40 without ER coil (NERC). PIDS contains any voxel where: (1) the diffusion signal increases despite an increase in b-value; and/or (2) apparent diffusion coefficient (ADC) is more than 3.0 µm2/ms (the ADC of pure water at 37 °C and it is physically implausible for any material to have a higher ADC). PIDS for transition zone (TZ) and peripheral zone (PZ) was calculated using an in-house MATLAB program. DWI images were quantitatively inspected for noise, motion, and distortion. T-test was used to compare the difference between PIDS levels in ERC versus NERC and ANOVA to compare the PIDS levels in the anatomic zones. The images were evaluated by a fellowship-trained radiologist in Abdominal Imaging with more than 10 years of experience in reading prostate MRI. This was tested only in prostate in this study. RESULTS: 80 patients (58 ± 8 years old, 80 men) were evaluated. The percentage of voxels exhibiting PIDS was 17.1 ± 8.1% for the ERC cohort and 22.2 ± 15.5% for the NERC cohort. PIDS for NERC versus ERC were not significantly different (p = 0.14). The apex and base showed similar percentages of PIDS in ERC (p = 0.30) and NERC (p = 0.86). The mid (13.8 ± 8.6%) in ERC showed lower values (p = 0.02) of PIDS compared to apex (19.9 ± 11.1%) and base (17.5 ± 8.3%). CONCLUSION: PIDS maps provide a spatially resolved quantitative quality assessment for prostate DWI. Average PIDS over the entire prostate were similar for the ERC and NERC cohorts, and did not differ significantly across prostate zones. However, for many of the patients, PIDS was focally much higher in specific prostate zones. PIDS assessment can guide Radiologist's evaluation of images and the development of improved DWI sequences.