Fast and High-Resolution T2 Mapping Based on Echo Merging Plus k-t Undersampling with Reduced Refocusing Flip Angles (TEMPURA) as Methods for Human Renal MRI.

PURPOSE: To develop a highly accelerated multi-echo spin-echo method, TEMPURA, for reducing the acquisition time and/or increasing spatial resolution for kidney T2 mapping. METHODS: TEMPURA merges several adjacent echoes into one k-space by either combining independent echoes or sharing one echo between k-spaces. The combined k-space is reconstructed based on compressed sensing theory. Reduced flip angles are used for the refocusing pulses, and the extended phase graph algorithm is used to correct the effects of indirect echoes. Two sequences were developed: a fast breath-hold sequence; and a high-resolution sequence. The performance was evaluated prospectively on a phantom, 16 healthy subjects, and two patients with different types of renal tumors. RESULTS: The fast TEMPURA method reduced the acquisition time from 3-5 min to one breath-hold (18 s). Phantom measurements showed that fast TEMPURA had a mean absolute percentage error (MAPE) of 8.2%, which was comparable to a standardized respiratory-triggered sequence (7.4%), but much lower than a sequence accelerated by purely k-t undersampling (21.8%). High-resolution TEMPURA reduced the in-plane voxel size from 3 × 3 to 1 × 1 mm2, resulting in improved visualization of the detailed anatomical structure. In vivo T2 measurements demonstrated good agreement (fast: MAPE = 1.3%-2.5%; high-resolution: MAPE = 2.8%-3.3%) and high correlation coefficients (fast: R = 0.85-0.98; high-resolution: 0.82-0.96) with the standardized method, outperforming k-t undersampling alone (MAPE = 3.3-4.5%, R = 0.57-0.59). CONCLUSION: TEMPURA provides fast and high-resolution renal T2 measurements. It has the potential to improve clinical throughput and delineate intratumoral heterogeneity and tissue habitats at unprecedented spatial resolution.

MRI assessment of seminal vesicle involvement by prostate cancer using T2 signal intensity and volume.

BACKGROUND: Seminal vesicle involvement (SVI) in patients with newly diagnosed prostate cancer is associated with high rates of treatment failure and tumor recurrence; correct identification of SVI allows for effective management decisions and surgical planning. METHODS: This single-center retrospective study analyzed MR images of the seminal vesicles from patients undergoing radical prostatectomy with confirmed T3b disease, comparing them to a control group without SVI matched for age and Gleason grade with a final stage of T2 or T3a. Seminal vesicles were segmented by an experienced uroradiologist, "raw" and bladder-normalized T2 signal intensity, as well as SV volume, were obtained. RESULTS: Among the 82 patients with SVI, 34 (41.6%) had unilateral invasion, and 48 (58.4%) had bilateral disease. There was no statistically significant difference in the degree of distension between normal and involved seminal vesicles (P = 0.08). Similarly, no statistically significant difference was identified in the raw SV T2 signal intensity (P = 0.09) between the groups. In the 159 patients analyzed, SVI was prospectively suspected in 10 of 82 patients (specificity, 100%; sensitivity, 12.2%). In all these cases, lesions macroscopically invaded the seminal vesicle, and the raw T2 signal intensity was significantly lower than that in the SVI and control groups (P = 0.02 and 0.01). CONCLUSION: While signal intensity measurements in T2-weighted images may provide insight into T3b disease, our findings suggest that this data alone is insufficient to reliably predict SVI, indicating the need for further investigation and complementary diagnostic approaches.

A scan-specific quality control acquisition for clinical whole-body (WB) MRI protocols.

OBJECTIVE: Image quality in whole-body MRI (WB-MRI) may be degraded by faulty radiofrequency (RF) coil elements or mispositioning of the coil arrays. Phantom-based quality control (QC) is used to identify broken RF coil elements but the frequency of these acquisitions is limited by scanner and staff availability. This work aimed to develop a scan-specific QC acquisition and processing pipeline to detect broken RF coil elements, which is sufficiently rapid to be added to the clinical WB-MRI protocol. The purpose of this is to improve the quality of WB-MRI by reducing the number of patient examinations conducted with suboptimal equipment. Approach: A rapid acquisition (14 seconds additional acquisition time per imaging station) was developed that identifies broken RF coil elements by acquiring images from each individual coil element and using the integral body coil. This acquisition was added to one centre's clinical WB-MRI protocol for one year (892 examinations) to evaluate the effect of this scan-specific QC. To demonstrate applicability in multi-centre imaging trials, the technique was also implemented on scanners from three manufacturers. Main Results: Over the course of the study RF coil elements were flagged as potentially broken on five occasions, with the faults confirmed in four of those cases. The method had a precision of 80 % and a recall of 100 % for detecting faulty RF coil elements. The coil array positioning measurements were consistent across scanners and have been used to define the expected variation in signal. Significance: The technique demonstrated here can identify faulty RF coil elements and positioning errors and is a practical addition to the clinical WB-MRI protocol. This approach was fully implemented on systems from three manufacturers and partially implemented on a third. It has potential to reduce the number of clinical examinations conducted with suboptimal hardware and improve image quality across multi-centre studies.

Improvements in Between-Vendor MRI Harmonization of Renal T2 Mapping using Stimulated Echo Compensation.

BACKGROUND: T2 mapping is valuable to evaluate pathophysiology in kidney disease. However, variations in T2 relaxation time measurements across MR scanners and vendors may occur requiring additional correction. PURPOSE: To harmonize renal T2 measurements between MR vendor platforms, and use an extended-phase-graph-based fitting method ("StimFit") to correct stimulated echoes and reduce between-vendor variations. STUDY TYPE: Prospective. SUBJECTS: 8 healthy "travelling" volunteers (37.5% female, 32 ± 6 years) imaged on four MRI systems across three vendors at four sites, 10 healthy volunteers (50% female, 32 ± 8 years) scanned multiple times on a given MR scanner for repeatability evaluation. ISMRM/NIST system phantom scanned for evaluation of T2 accuracy. FIELD STRENGTH/SEQUENCE: 3T, multiecho spin-echo sequence. ASSESSMENT: T2 images fit using conventional monoexponential fitting and "StimFit." Mean absolute percentage error (MAPE) of phantom measurements with reference T2 values. Average cortex and medulla T2 values compared between MR vendors, with masks obtained from T2 -weighted images and T1 maps. Full-width-at-half-maximum (FWHM) T2 distributions to evaluate local homogeneity of measurements. STATISTICAL TESTS: Coefficient of variation (CV), linear mixed-effects model, analysis of variance, student's t-tests, Bland-Altman plots, P-value <0.05 considered statistically significant. RESULTS: In the ISMRM/NIST phantom, "StimFit" reduced the MAPE from 4.9%, 9.1%, 24.4%, and 18.1% for the four sites (three vendors) to 3.3%, 3.0%, 6.6%, and 4.1%, respectively. In vivo, there was a significant difference in kidney T2 measurements between vendors using a monoexponential fit, but not with "StimFit" (P = 0.86 and 0.92, cortex and medulla, respectively). The intervendor CVs of T2 measures were reduced from 8.0% to 2.6% (cortex) and 7.1% to 2.8% (medulla) with StimFit, resulting in no significant differences for the CVs of intravendor repeat acquisitions (P = 0.13 and 0.05). "StimFit" significantly reduced the FWHM of T2 distributions in the cortex and whole kidney. DATA CONCLUSION: Stimulated-echo correction reduces renal T2 variation across MR vendor platforms. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Mammography Breast Cancer Screening Triage Using Deep Learning: A UK Retrospective Study.

Background Breast screening enables early detection of cancers; however, most women have normal mammograms, resulting in repetitive and resource-intensive reading tasks. Purpose To investigate if deep learning (DL) algorithms can be used to triage mammograms by identifying normal results to reduce workload or flag cancers that may be overlooked. Materials and Methods In this retrospective study, three commercial DL algorithms were investigated using consecutive mammograms from two UK Breast Screening Program sites from January 2015 to December 2017 and January 2017 to December 2018 on devices from two mammography vendors. Normal mammograms with a 3-year follow-up and histopathologically proven cancer detected at screening, the subsequent round, or in the 3-year interval were included. Two algorithm thresholds were set: in scenario A, 99.0% sensitivity for rule-out triage to a lone reader, and in scenario B, approximately 1.0% additional recall providing a rule-in triage for further assessment. Both thresholds were then applied to the screening workflow in scenario C. The sensitivity and specificity were used to assess the overall predictive performance of each DL algorithm. Results The data set comprised 78 849 patients (median age, 59 years [IQR, 53-63 years]) and 887 screening-detected, 439 interval, and 688 subsequent screening round-detected cancers. In scenario A (rule-out triage), models DL-1, DL-2, and DL-3 triaged 35.0% (27 565 of 78 849), 53.2% (41 937 of 78 849), and 55.6% (43 869 of 78 849) of mammograms, respectively, with 0.0% (0 of 887) to 0.1% (one of 887) of screening-detected cancers undetected. In scenario B, DL algorithms triaged in 4.6% (20 of 439) to 8.2% (36 of 439) of interval and 5.2% (36 of 688) to 6.1% (42 of 688) of subsequent-round cancers when applied after the routine double-reading workflow. Combining both approaches in scenario C resulted in an overall noninferior specificity (difference, -0.9%; P < .001) and superior sensitivity (difference, 2.7%; P < .001) for the adaptive workflow compared with routine double reading for all three algorithms. Conclusion Rule-out and rule-in DL-adapted triage workflows can improve the efficiency and efficacy of mammography breast cancer screening. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Nishikawa and Lu in this issue.

Quantification and reduction of cross-vendor variation in multicenter DWI MR imaging: results of the Cancer Core Europe imaging task force.

OBJECTIVES: In the Cancer Core Europe Consortium (CCE), standardized biomarkers are required for therapy monitoring oncologic multicenter clinical trials. Multiparametric functional MRI and particularly diffusion-weighted MRI offer evident advantages for noninvasive characterization of tumor viability compared to CT and RECIST. A quantification of the inter- and intraindividual variation occurring in this setting using different hardware is missing. In this study, the MRI protocol including DWI was standardized and the residual variability of measurement parameters quantified. METHODS: Phantom and volunteer measurements (single-shot T2w and DW-EPI) were performed at the seven CCE sites using the MR hardware produced by three different vendors. Repeated measurements were performed at the sites and across the sites including a traveling volunteer, comparing qualitative and quantitative ROI-based results including an explorative radiomics analysis. RESULTS: For DWI/ADC phantom measurements using a central post-processing algorithm, the maximum deviation could be decreased to 2%. However, there is no significant difference compared to a decentralized ADC value calculation at the respective MRI devices. In volunteers, the measurement variation in 2 repeated scans did not exceed 11% for ADC and is below 20% for single-shot T2w in systematic liver ROIs. The measurement variation between sites amounted to 20% for ADC and < 25% for single-shot T2w. Explorative radiomics classification experiments yield better results for ADC than for single-shot T2w. CONCLUSION: Harmonization of MR acquisition and post-processing parameters results in acceptable standard deviations for MR/DW imaging. MRI could be the tool in oncologic multicenter trials to overcome the limitations of RECIST-based response evaluation. KEY POINTS: • Harmonizing acquisition parameters and post-processing homogenization, standardized protocols result in acceptable standard deviations for multicenter MR-DWI studies. • Total measurement variation does not to exceed 11% for ADC in repeated measurements in repeated MR acquisitions, and below 20% for an identical volunteer travelling between sites. • Radiomic classification experiments were able to identify stable features allowing for reliable discrimination of different physiological tissue samples, even when using heterogeneous imaging data.

A Phase II study of neoadjuvant axitinib for reducing the extent of venous tumour thrombus in clear cell renal cell cancer with venous invasion (NAXIVA).

BACKGROUND: Surgery for renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the renal vein (RV) and/or inferior vena cava (IVC) has high peri-surgical morbidity/mortality. NAXIVA assessed the response of VTT to axitinib, a potent tyrosine kinase inhibitor. METHODS: NAXIVA was a single-arm, multi-centre, Phase 2 study. In total, 20 patients with resectable clear cell RCC and VTT received upto 8 weeks of pre-surgical axitinib. The primary endpoint was percentage of evaluable patients with VTT improvement by Mayo level on MRI. Secondary endpoints were percentage change in surgical approach and VTT length, response rate (RECISTv1.1) and surgical morbidity. RESULTS: In all, 35% (7/20) patients with VTT had a reduction in Mayo level with axitinib: 37.5% (6/16) with IVC VTT and 25% (1/4) with RV-only VTT. No patients had an increase in Mayo level. In total, 75% (15/20) of patients had a reduction in VTT length. Overall, 41.2% (7/17) of patients who underwent surgery had less invasive surgery than originally planned. Non-responders exhibited lower baseline microvessel density (CD31), higher Ki67 and exhausted or regulatory T-cell phenotype. CONCLUSIONS: NAXIVA provides the first Level II evidence that axitinib downstages VTT in a significant proportion of patients leading to reduction in the extent of surgery. CLINICAL TRIAL REGISTRATION: NCT03494816.

Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.

Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.

Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.

Hyperpolarised magnetic resonance imaging (HP 13C-MRI) is an emerging clinical technique to detect [1-13C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-13C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/intermediate-risk population by correlating [1-13C]lactate labelling on MRI with the percentage of Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, we show that HP 13C-MRI predominantly measures metabolism in the epithelial compartment of the tumour, rather than the stroma. MRI-derived tumour [1-13C]lactate labelling correlated with epithelial mRNA expression of the enzyme lactate dehydrogenase (LDHA and LDHB combined), and the ratio of lactate transporter expression between the epithelial and stromal compartments (epithelium-to-stroma MCT4). We observe similar changes in MCT4, LDHA, and LDHB between tumours with primary Gleason patterns 3 and 4 in an independent TCGA cohort. Therefore, HP 13C-MRI can metabolically phenotype clinically significant disease based on underlying metabolic differences in the epithelial and stromal tumour compartments.

Dynamic biomarker and imaging changes from a phase II study of pre- and post-surgical sunitinib.

OBJECTIVE: To explore translational biological and imaging biomarkers for sunitinib treatment before and after debulking nephrectomy in the NeoSun (European Union Drug Regulating Authorities Clinical Trials Database [EudraCT] number: 2005-004502-82) single-centre, single-arm, single-agent, Phase II trial. PATIENTS AND METHODS: Treatment-naïve patients with metastatic renal cell carcinoma (mRCC) received 50 mg once daily sunitinib for 12 days pre-surgically, then post-surgery on 4 week-on, 2 week-off, repeating 6-week cycles until disease progression in a single arm phase II trial. Structural and dynamic contrast-enhanced magnet resonance imaging (DCE-MRI) and research blood sampling were performed at baseline and after 12 days. Computed tomography imaging was performed at baseline and post-surgery then every two cycles. The primary endpoint was objective response rate (Response Evaluation Criteria In Solid Tumors [RECIST]) excluding the resected kidney. Secondary endpoints included changes in DCE-MRI of the tumour following pre-surgery sunitinib, overall survival (OS), progression-free survival (PFS), response duration, surgical morbidity/mortality, and toxicity. Translational and imaging endpoints were exploratory. RESULTS: A total of 14 patients received pre-surgery sunitinib, 71% (10/14) took the planned 12 doses. All underwent nephrectomy, and 13 recommenced sunitinib postoperatively. In all, 58.3% (seven of 12) of patients achieved partial or complete response (PR or CR) (95% confidence interval 27.7-84.8%). The median OS was 33.7 months and median PFS was 15.7 months. Amongst those achieving a PR or CR, the median response duration was 8.7 months. No unexpected surgical complications, sunitinib-related toxicities, or surgical delays occurred. Within the translational endpoints, pre-surgical sunitinib significantly increased necrosis, and reduced cluster of differentiation-31 (CD31), Ki67, circulating vascular endothelial growth factor-C (VEGF-C), and transfer constant (KTrans , measured using DCE-MRI; all P < 0.05). There was a trend for improved OS in patients with high baseline plasma VEGF-C expression (P = 0.02). Reduction in radiological tumour volume after pre-surgical sunitinib correlated with high percentage of solid tumour components at baseline (Spearman's coefficient ρ = 0.69, P = 0.02). Conversely, the percentage tumour volume reduction correlated with lower baseline percentage necrosis (coefficient = -0.51, P = 0.03). CONCLUSION: Neoadjuvant studies such as the NeoSun can safely and effectively explore translational biological and imaging endpoints.

Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma.

PURPOSE: To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. METHOD: Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: 2005-004502-82) were imaged before starting treatment, and after 12 days of sunitinib therapy using morphological MRI sequences, advanced diffusion-weighted imaging, measurements of R2* (related to hypoxia) and dynamic contrast-enhanced imaging. Following nephrectomy, participants continued treatment and were followed-up with contrast-enhanced CT. Changes in imaging parameters before and after sunitinib were assessed with the non-parametric Wilcoxon signed-rank test and the log-rank test was used to assess effects on survival. RESULTS: 12 participants fulfilled the inclusion criteria. After 12 days, the solid and necrotic tumor volumes decreased by 28% and 17%, respectively (p = 0.04). However, tumor-volume reduction did not correlate with progression-free or overall survival (PFS/OS). Sunitinib therapy resulted in a reduction in median solid tumor diffusivity D from 1298x10-6 to 1200x10-6mm2/s (p = 0.03); a larger decrease was associated with a better RECIST response (p = 0.02) and longer PFS (p = 0.03) on the log-rank test. An increase in R2* from 19 to 28s-1 (p = 0.001) was observed, paralleled by a decrease in Ktrans from 0.415 to 0.305min-1 (p = 0.01) and a decrease in perfusion fraction from 0.34 to 0.19 (p<0.001). CONCLUSIONS: Physiological imaging confirmed efficacy of the anti-angiogenic agent 12 days after initiating therapy and demonstrated response to treatment. The change in diffusivity shortly after starting pre-surgical sunitinib correlated to PFS in mRCC undergoing nephrectomy, however, no parameter predicted OS. TRIAL REGISTRATION: EudraCtNo: 2005-004502-82.

Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients.

Hyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1-13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7-11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5-6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. SIGNIFICANCE: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7-11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.

Multiparametric MRI of early tumor response to immune checkpoint blockade in metastatic melanoma.

BACKGROUND: Immune checkpoint inhibitors are now standard of care treatment for many cancers. Treatment failure in metastatic melanoma is often due to tumor heterogeneity, which is not easily captured by conventional CT or tumor biopsy. The aim of this prospective study was to investigate early microstructural and functional changes within melanoma metastases following immune checkpoint blockade using multiparametric MRI. METHODS: Fifteen treatment-naïve metastatic melanoma patients (total 27 measurable target lesions) were imaged at baseline and following 3 and 12 weeks of treatment on immune checkpoint inhibitors using: T2-weighted imaging, diffusion kurtosis imaging, and dynamic contrast-enhanced MRI. Treatment timepoint changes in tumor cellularity, vascularity, and heterogeneity within individual metastases were evaluated and correlated to the clinical outcome in each patient based on Response Evaluation Criteria in Solid Tumors V.1.1 at 1 year. RESULTS: Differential tumor growth kinetics in response to immune checkpoint blockade were measured in individual metastases within the same patient, demonstrating significant intertumoral heterogeneity in some patients. Early detection of tumor cell death or cell loss measured by a significant increase in the apparent diffusivity (Dapp) (p<0.05) was observed in both responding and pseudoprogressive lesions after 3 weeks of treatment. Tumor heterogeneity, as measured by apparent diffusional kurtosis (Kapp), was consistently higher in the pseudoprogressive and true progressive lesions, compared with the responding lesions throughout the first 12 weeks of treatment. These preceded tumor regression and significant tumor vascularity changes (Ktrans, ve, and vp) detected after 12 weeks of immunotherapy (p<0.05). CONCLUSIONS: Multiparametric MRI demonstrated potential for early detection of successful response to immune checkpoint inhibitors in metastatic melanoma.

Investigating the relationship between diffusion kurtosis tensor imaging (DKTI) and histology within the normal human brain.

Measurements of water diffusion with MRI have been used as a biomarker of tissue microstructure and heterogeneity. In this study, diffusion kurtosis tensor imaging (DKTI) of the brain was undertaken in 10 healthy volunteers at a clinical field strength of 3 T. Diffusion and kurtosis metrics were measured in regions-of-interest on the resulting maps and compared with quantitative analysis of normal post-mortem tissue histology from separate age-matched donors. White matter regions showed low diffusion (0.60 ± 0.04 × 10-3 mm2/s) and high kurtosis (1.17 ± 0.06), consistent with a structured heterogeneous environment comprising parallel neuronal fibres. Grey matter showed intermediate diffusion (0.80 ± 0.02 × 10-3 mm2/s) and kurtosis (0.82 ± 0.05) values. An important finding is that the subcortical regions investigated (thalamus, caudate and putamen) showed similar diffusion and kurtosis properties to white matter. Histological staining of the subcortical nuclei demonstrated that the predominant grey matter was permeated by small white matter bundles, which could account for the similar kurtosis to white matter. Quantitative histological analysis demonstrated higher mean tissue kurtosis and vector standard deviation values for white matter (1.08 and 0.81) compared to the subcortical regions (0.34 and 0.59). Mean diffusion on DKTI was positively correlated with tissue kurtosis (r = 0.82, p < 0.05) and negatively correlated with vector standard deviation (r = -0.69, p < 0.05). This study demonstrates how DKTI can be used to study regional structural variations in the cerebral tissue microenvironment and could be used to probe microstructural changes within diseased tissue in the future.

Highly accelerated subtractive femoral non-contrast-enhanced MRA using compressed sensing with k-space subtraction, phase and intensity correction.

PURPOSE: To develop an improved reconstruction method, k-space subtraction with phase and intensity correction (KSPIC), for highly accelerated, subtractive, non-contrast-enhanced MRA. METHODS: The KSPIC method is based on k-space subtraction of complex raw data. It applies a phase-correction procedure to restore the polarity of negative signals caused by subtraction and an intensity-correction procedure to improve background suppression and thereby sparsity. Ten retrospectively undersampled data sets and 10 groups of prospectively undersampled data sets were acquired in 12 healthy volunteers. The performance of KSPIC was compared with another improved reconstruction based on combined magnitude subtraction, as well as with conventional k-space subtraction reconstruction and magnitude subtraction reconstruction, both using quantitative metrics and using subjective quality scoring. RESULTS: In the quantitative evaluation, KSPIC had the best performance in terms of peak SNR, structural similarity index measure, contrast-to-noise ratio of artery-to-background and sharpness, especially at high acceleration factors. The KSPIC method also had the highest subjective scores for all acceleration factors in terms of vessel delineation, image noise and artifact, and background contamination. The acquisition can be accelerated by a factor of 20 without significant decreases of subjective scores. The optimal size of the phase-correction region was found to be 12-20 pixels in this study. CONCLUSION: Compared with combined magnitude subtraction and conventional reconstructions, KSPIC has the best performance in all of the quantitative and qualitative measurements, permitting good image quality to be maintained up to higher accelerations. The KSPIC method has the potential to further reduce the acquisition time of subtractive MRA for clinical examinations.

MRI features of the normal prostatic peripheral zone: the relationship between age and signal heterogeneity on T2WI, DWI, and DCE sequences.

OBJECTIVES: To assess the multiparametric MRI (mpMRI) appearances of normal peripheral zone (PZ) across age groups in a biopsy-naïve population, where prostate cancer (PCa) was subsequently excluded, and propose a scoring system for background PZ changes. METHODS: This retrospective study included 175 consecutive biopsy-naïve patients (40-74 years) referred with a suspicion of PCa, but with subsequent negative investigations. Patients were grouped by age into categories ≤ 54, 55-59, 60-64, and ≥ 65 years. MpMRI sequences (T2-weighted imaging [T2WI], diffusion-weighted imaging [DWI]/apparent diffusion coefficient [ADC], and dynamic contrast-enhanced imaging [DCE]) were independently evaluated by two uro-radiologists on a proposed 4-point grading scale for background change on each sequence, wherein score 1 mirrored PIRADS-1 change and score 4 represented diffuse background change. Peripheral zone T2WI signal intensity and ADC values were also analyzed for trends relating to age. RESULTS: There was a negative correlation between age and assigned background PZ scores for each mpMRI sequence: T2WI: r = - 0.52, DWI: r = - 0.49, DCE: r = - 0.45, p < 0.001. Patients aged ≤ 54 years had mean scores of 3.0 (T2WI), 2.7 (DWI), and 3.1 (DCE), whilst patients ≥ 65 years had significantly lower mean scores of 1.7, 1.4, and 1.9, respectively. There was moderate inter-reader agreement for all scores (range κ = 0.43-0.58). Statistically significant positive correlations were found for age versus normalized T2WI signal intensity (r = 0.2, p = 0.009) and age versus ADC values (r = 0.33, p = 0.001). CONCLUSION: The normal PZ in younger patients (≤ 54 years) demonstrates significantly lower T2WI signal intensity, lower ADC values, and diffuse enhancement on DCE, which may hinder diagnostic interpretation in these patients. The proposed standardized PZ background scoring system may help convey the potential for diagnostic uncertainty to clinicians. KEY POINTS: • Significant, positive correlations were found between increasing age and higher normalized T2-weighted signal intensity and mean ADC values of the prostatic peripheral zone. • Younger men exhibit lower T2-weighted imaging signal intensity, lower ADC values, and diffuse enhancement on dynamic contrast-enhanced imaging, which may hinder MRI interpretation. • A scoring system is proposed which aims towards a standardized assessment of the normal background PZ. This may help convey the potential for diagnostic uncertainty to clinicians.

Subtractive NCE-MRA: Improved background suppression using robust regression-based weighted subtraction.

PURPOSE: To correct the intensity difference of static background signal between bright blood images and dark blood images in subtractive non-contrast-enhanced MR angiography using robust regression, thereby improving static background signal suppression on subtracted angiograms. METHODS: Robust regression (RR), using iteratively reweighted least squares, is used to calculate the regression coefficient of background tissues from a scatter plot showing the voxel intensity of bright blood images versus dark blood images. The weighting function is based on either the Euclidean distance from the estimated regression line or the deviation angle. Results from RR using the deviation angle (RRDA), conventional RR using the Euclidean distance, and ordinary leastsquares regression were compared with reference values determined manually by two observers. Performance was evaluated over studies using different sequences, including 36 thoracic flow-sensitive dephasing data sets, 13 iliac flow-sensitive dephasing data sets, and 26 femoral fresh blood imaging data sets. RESULTS: RR deviation angle achieved robust and accurate performance in all types of images, with small bias, small mean absolute error, and high-correlation coefficients with reference values. Background tissues, such as muscle, veins, and bladder, were suppressed while the vascular signal was preserved. Euclidean distance gave good performance for thoracic and iliac flow-sensitive dephasing, but could not suppress background tissues in femoral fresh blood imaging. Ordinary least squares regression was sensitive to outliers and overestimated regression coefficients in thoracic flow-sensitive dephasing. CONCLUSION: Weighted subtraction using RR was able to acquire the regression coefficients of background signal and improve background suppression of subtractive non-contrast-enhanced MR angiography techniques. RR deviation angle has the most robust and accurate overall performance among three regression methods.

Three-Dimensional Printed Molds for Image-Guided Surgical Biopsies: An Open Source Computational Platform.

PURPOSE: Spatial heterogeneity of tumors is a major challenge in precision oncology. The relationship between molecular and imaging heterogeneity is still poorly understood because it relies on the accurate coregistration of medical images and tissue biopsies. Tumor molds can guide the localization of biopsies, but their creation is time consuming, technologically challenging, and difficult to interface with routine clinical practice. These hurdles have so far hindered the progress in the area of multiscale integration of tumor heterogeneity data. METHODS: We have developed an open-source computational framework to automatically produce patient-specific 3-dimensional-printed molds that can be used in the clinical setting. Our approach achieves accurate coregistration of sampling location between tissue and imaging, and integrates seamlessly with clinical, imaging, and pathology workflows. RESULTS: We applied our framework to patients with renal cancer undergoing radical nephrectomy. We created personalized molds for 6 patients, obtaining Dice similarity coefficients between imaging and tissue sections ranging from 0.86 to 0.96 for tumor regions and between 0.70 and 0.76 for healthy kidneys. The framework required minimal manual intervention, producing the final mold design in just minutes, while automatically taking into account clinical considerations such as a preference for specific cutting planes. CONCLUSION: Our work provides a robust and automated interface between imaging and tissue samples, enabling the development of clinical studies to probe tumor heterogeneity on multiple spatial scales.

Simultaneous MRI water-fat separation and quantitative susceptibility mapping of carotid artery plaque pre- and post-ultrasmall superparamagnetic iron oxide-uptake.

PURPOSE: Imaging carotid artery plaques to identify features of vulnerability typically requires a multicontrast MRI protocol. The identification of regions of inflammation with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles requires separate pre- and postcontrast scans. We propose a method of joint water-fat separation and quantitative susceptibility mapping (QSM) to aid classification of atherosclerotic plaques and offer a positive contrast mechanism in USPIO-imaging. METHODS: Ten healthy volunteers (3 women and 7 men; aged, 30.7 ± 10.7 years) were imaged at 1.5T to develop an acquisition and postprocessing protocol. Five patients (1 woman and 4 men; mean age, 71 ± 7.5 years) with moderate to severe luminal stenosis were imaged pre- and postadministration of a USPIO contrast agent. We used a multiecho gradient echo acquisition to perform water/fat separation and subsequently QSM. The results were compared with a conventional multicontrast MRI protocol, CT images, and histopathology data. RESULTS: In the volunteer scans, a multiecho gradient echo acquisition with bipolar readout gradients demonstrated to be a reliable acquisition methodology to produce high-quality susceptibility maps in conjunction with the proposed postprocessing methodology. In the patient study, water/fat separation provided a tool to identify lipid-rich necrotic cores and QSM provided a qualitative and quantitative evaluation of plaque features and positive contrast when evaluating USPIO uptake. Plaque calcification could be identified by strong diamagnetism (-1.27 ± 0.71 ppm), while USPIO uptake demonstrated a strong paramagnetism (1.32 ± 0.61 ppm). CONCLUSION: QSM was able to identify multiple plaque features in a single acquisition, providing positive contrast for plaques demonstrating USPIO uptake and negative contrast for calcification.