Expanding the Treatable Imaging Profile in Patients With Large Ischemic Stroke: Subanalysis From a Randomized Clinical Trial.

BACKGROUND: We aimed to examine the boundary of the ischemic core volume in patients undergoing endovascular thrombectomy (EVT) versus those receiving medical management to determine the minimum optimal size for favorable treatment outcomes. METHODS: This is a prespecified substudy of the RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Large Ischemic Core Trial). Patients with large vessel occlusion were enrolled between November 2018 and September 2021 with a National Institutes of Health Stroke Scale score of at least 6 on admission and an Alberta Stroke Program Early Computed Tomography Score value of 3 to 5. We investigated the correlation between optimal quantified ischemic core volume, assessed solely using magnetic resonance diffusion-weighted imaging, and functional outcomes (modified Rankin Scale score, 0-3) at 90 days by predictive marginal plots. Final infarct volume and safety outcomes (symptomatic intracerebral hemorrhage and mortality) were also assessed. RESULTS: Of the 203 cases, 168 patients (85 in the EVT group versus 83 in the medical management group) were included. The median (interquartile range) core volume was 94 (65-160) mL in patients with EVT and 115 (71-141) mL in the medical management group (P=0.72). The predictive marginal probabilities of the 2 groups intersected at 128 mL for estimating functional outcomes. Symptomatic intracerebral hemorrhage and mortality within 90 days had overlay margins through all core volumes in both groups. The median final infarct volume (interquartile range) was smaller in the EVT group (142 [80-223] mL versus 211 [123-289] mL in the medical management group; P<0.001). CONCLUSIONS: In this prespecified analysis of a randomized clinical trial involving patients with large ischemic strokes, patients with an estimated core volume of up to 128 mL on diffusion-weighted imaging benefit from EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03702413.

High-resolution diffusion magnetic resonance imaging and spatial-transcriptomic in developing mouse brain.

Brain development is a highly complex process regulated by numerous genes at the molecular and cellular levels. Brain tissue exhibits serial microstructural changes during the development process. High-resolution diffusion magnetic resonance imaging (dMRI) affords a unique opportunity to probe these changes in the developing brain non-destructively. In this study, we acquired multi-shell dMRI datasets at 32 µm isotropic resolution to investigate the tissue microstructure alterations, which we believe to be the highest spatial resolution dMRI datasets obtained for postnatal mouse brains. We adapted the Allen Developing Mouse Brain Atlas (ADMBA) to integrate quantitative MRI metrics and spatial transcriptomics. Diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and neurite orientation dispersion and density imaging (NODDI) metrics were used to quantify brain development at different postnatal days. We demonstrated that the differential evolutions of fiber orientation distributions contribute to the distinct development patterns in white matter (WM) and gray matter (GM). Furthermore, the genes enriched in the nervous system that regulate brain structure and function were expressed in spatial correlation with age-matched dMRI. This study is the first one providing high-resolution dMRI, including DTI, DKI, and NODDI models, to trace mouse brain microstructural changes in WM and GM during postnatal development. This study also highlighted the genotype-phenotype correlation of spatial transcriptomics and dMRI, which may improve our understanding of brain microstructure changes at the molecular level.

A "glympse" into neurodegeneration: Diffusion MRI and cerebrospinal fluid aquaporin-4 for the assessment of glymphatic system in Alzheimer's disease and other dementias.

The glymphatic system (GS) is a whole-brain perivascular network, consisting of three compartments: the periarterial and perivenous spaces and the interposed brain parenchyma. GS dysfunction has been implicated in neurodegenerative diseases, particularly Alzheimer's disease (AD). So far, comprehensive research on GS in humans has been limited by the absence of easily accessible biomarkers. Recently, promising non-invasive methods based on magnetic resonance imaging (MRI) along with aquaporin-4 (AQP4) quantification in the cerebrospinal fluid (CSF) were introduced for an indirect assessment of each of the three GS compartments. We recruited 111 consecutive subjects presenting with symptoms suggestive of degenerative cognitive decline, who underwent 3 T MRI scanning including multi-shell diffusion-weighted images. Forty nine out of 111 also underwent CSF examination with quantification of CSF-AQP4. CSF-AQP4 levels and MRI measures-including perivascular spaces (PVS) counts and volume fraction (PVSVF), white matter free water fraction (FW-WM) and mean kurtosis (MK-WM), diffusion tensor imaging analysis along the perivascular spaces (DTI-ALPS) (mean, left and right)-were compared among patients with AD (n = 47) and other neurodegenerative diseases (nAD = 24), patients with stable mild cognitive impairment (MCI = 17) and cognitively unimpaired (CU = 23) elderly people. Two runs of analysis were conducted, the first including all patients; the second after dividing both nAD and AD patients into two subgroups based on gray matter atrophy as a proxy of disease stage. Age, sex, years of education, and scanning time were included as confounding factors in the analyses. Considering the whole cohort, patients with AD showed significantly higher levels of CSF-AQP4 (exp(b) = 2.05, p = .005) and FW-WM FW-WM (exp(b) = 1.06, p = .043) than CU. AQP4 levels were also significantly higher in nAD in respect to CU (exp(b) = 2.98, p < .001). CSF-AQP4 and FW-WM were significantly higher in both less atrophic AD (exp(b) = 2.20, p = .006; exp(b) = 1.08, p = .019, respectively) and nAD patients (exp(b) = 2.66, p = .002; exp(b) = 1.10, p = .019, respectively) compared to CU subjects. Higher total (exp(b) = 1.59, p = .013) and centrum semiovale PVS counts (exp(b) = 1.89, p = .016), total (exp(b) = 1.50, p = .036) and WM PVSVF (exp(b) = 1.89, p = .005) together with lower MK-WM (exp(b) = 0.94, p = .006), mean and left ALPS (exp(b) = 0.91, p = .043; exp(b) = 0.88, p = .010 respectively) were observed in more atrophic AD patients in respect to CU. In addition, more atrophic nAD patients exhibited higher levels of AQP4 (exp(b) = 3.39, p = .002) than CU. Our results indicate significant changes in putative MRI biomarkers of GS and CSF-AQP4 levels in AD and in other neurodegenerative dementias, suggesting a close interaction between glymphatic dysfunction and neurodegeneration, particularly in the case of AD. However, the usefulness of some of these biomarkers as indirect and standalone indices of glymphatic activity may be hindered by their dependence on disease stage and structural brain damage.

Automatic deep learning segmentation of the hippocampus on high-resolution diffusion magnetic resonance imaging and its application to the healthy lifespan.

Diffusion tensor imaging (DTI) can provide unique contrast and insight into microstructural changes with age or disease of the hippocampus, although it is difficult to measure the hippocampus because of its comparatively small size, location, and shape. This has been markedly improved by the advent of a clinically feasible 1-mm isotropic resolution 6-min DTI protocol at 3 T of the hippocampus with limited brain coverage of 20 axial-oblique slices aligned along its long axis. However, manual segmentation is too laborious for large population studies, and it cannot be automatically segmented directly on the diffusion images using traditional T1 or T2 image-based methods because of the limited brain coverage and different contrast. An automatic method is proposed here that segments the hippocampus directly on high-resolution diffusion images based on an extension of well-known deep learning architectures like UNet and UNet++ by including additional dense residual connections. The method was trained on 100 healthy participants with previously performed manual segmentation on the 1-mm DTI, then evaluated on typical healthy participants (n = 53), yielding an excellent voxel overlap with a Dice score of ~ 0.90 with manual segmentation; notably, this was comparable with the inter-rater reliability of manually delineating the hippocampus on diffusion magnetic resonance imaging (MRI) (Dice score of 0.86). This method also generalized to a different DTI protocol with 36% fewer acquisitions. It was further validated by showing similar age trajectories of volumes, fractional anisotropy, and mean diffusivity from manual segmentations in one cohort (n = 153, age 5-74 years) with automatic segmentations from a second cohort without manual segmentations (n = 354, age 5-90 years). Automated high-resolution diffusion MRI segmentation of the hippocampus will facilitate large cohort analyses and, in future research, needs to be evaluated on patient groups.

R2* mapping and reduced field-of-view diffusion-weighted imaging for preoperative assessment of nonenlarged lymph node metastasis in rectal cancer.

The aim of the current study is to investigate the diagnostic value of R2* mapping versus reduced field-of-view diffusion-weighted imaging (rDWI) of the primary lesion of rectal cancer for preoperative prediction of nonenlarged lymph node metastasis (NLNM). Eighty-one patients with pathologically confirmed rectal cancer underwent preoperative R2* mapping and rDWI sequences before total mesorectal excisions and accompanying regional lymph node dissections. Two radiologists independently performed whole-tumor measurements of R2* and apparent diffusion coefficient (ADC) parameters on primary lesions of rectal cancer. Patients were divided into positive (NLNM+) and negative (NLNM-) groups based on their pathological analysis. The tumor location, maximum diameter of the tumor, and maximum short diameter of the lymph node were assessed. R2* and ADC, pT stage, tumor grade, status of mesorectal fascia, and extramural vascular invasion were also studied for their potential relationships with NLNM using multivariate logistic regression analysis. The NLNM+ group had significantly higher R2* (43.56 ± 8.43 vs. 33.87 ± 9.57, p < 0.001) and lower ADC (1.00 ± 0.13 vs. 1.06 ± 0.22, p = 0.036) than the NLNM- group. R2* and ADC were correlated to lymph node metastasis (r = 0.510, p < 0.001 for R2*; r = -0.235, p = 0.035 for ADC). R2* and ADC showed good and moderate diagnostic abilities in the assessment of NLNM status with corresponding area-under-the-curve values of 0.795 and 0.636. R2* provided a significantly better diagnostic performance compared with ADC for the prediction of NLNM status (z = 1.962, p = 0.0498). The multivariate logistic regression analysis demonstrated that R2* was a compelling factor of lymph node metastasis (odds ratio = 56.485, 95% confidence interval: 5.759-554.013; p = 0.001). R2* mapping had significantly higher diagnostic performance than rDWI from the primary tumor of rectal cancer in the prediction of NLNM status.

Magnetic resonance imaging of anal cancer: tumor characteristics and early prediction of treatment outcome.

PURPOSE: To analyze tumor characteristics derived from pelvic magnetic resonance imaging (MRI) of patients with squamous cell carcinoma of the anus (SCCA) before and during chemoradiotherapy (CRT), and to compare the changes in these characteristics between scans of responders vs. nonresponders to CRT. METHODS: We included 52 patients with a pelvic 3T MRI scan prior to CRT (baseline scan); 39 of these patients received an additional scan during week 2 of CRT (second scan). Volume, diameter, extramural tumor depth (EMTD), and external anal sphincter infiltration (EASI) of the tumor were assessed. Mean, kurtosis, skewness, standard deviation (SD), and entropy values were extracted from apparent diffusion coefficient (ADC) histograms. The main outcome was locoregional treatment failure. Correlations were evaluated with Wilcoxon's signed rank-sum test and Pearson's correlation coefficient, quantile regression, univariate logistic regression, and area under the ROC curve (AUC) analyses. RESULTS: In isolated analyses of the baseline and second MRI scans, none of the characteristics were associated with outcome. Comparison between the scans showed significant changes in several characteristics: volume, diameter, EMTD, and ADC skewness decreased in the second scan, although the mean ADC increased. Small decreases in volume and diameter were associated with treatment failure, and these variables had the highest AUC values (0.73 and 0.76, respectively) among the analyzed characteristics. CONCLUSION: Changes in tumor volume and diameter in an early scan during CRT could represent easily assessable imaging-based biomarkers to eliminate the need for analysis of more complex MRI characteristics.

Executive functioning, behavior, and white matter microstructure in the chronic phase after pediatric mild traumatic brain injury: results from the adolescent brain cognitive development study.

BACKGROUND: Mild traumatic brain injury (mTBI) is common in children. Long-term cognitive and behavioral outcomes as well as underlying structural brain alterations following pediatric mTBI have yet to be determined. In addition, the effect of age-at-injury on long-term outcomes is largely unknown. METHODS: Children with a history of mTBI (n = 406; Mage = 10 years, SDage = 0.63 years) who participated in the Adolescent Brain Cognitive Development (ABCD) study were matched (1:2 ratio) with typically developing children (TDC; n = 812) and orthopedic injury (OI) controls (n = 812). Task-based executive functioning, parent-rated executive functioning and emotion-regulation, and self-reported impulsivity were assessed cross-sectionally. Regression models were used to examine the effect of mTBI on these domains. The effect of age-at-injury was assessed by comparing children with their first mTBI at either 0-3, 4-7, or 8-10 years to the respective matched TDC controls. Fractional anisotropy (FA) and mean diffusivity (MD), both MRI-based measures of white matter microstructure, were compared between children with mTBI and controls. RESULTS: Children with a history of mTBI displayed higher parent-rated executive dysfunction, higher impulsivity, and poorer self-regulation compared to both control groups. At closer investigation, these differences to TDC were only present in one respective age-at-injury group. No alterations were found in task-based executive functioning or white matter microstructure. CONCLUSIONS: Findings suggest that everyday executive function, impulsivity, and emotion-regulation are affected years after pediatric mTBI. Outcomes were specific to the age at which the injury occurred, suggesting that functioning is differently affected by pediatric mTBI during vulnerable periods. Groups did not differ in white matter microstructure.

Diffusion-Weighted MRI of the Fetal Brain in Fetal Growth Restriction With Maternal Preeclampsia or Gestational Hypertension.

BACKGROUND: The fetal neurodevelopmental microstructural alterations of intrauterine exposure to preeclampsia (PE) or gestational hypertension (GH) remain unknown. PURPOSE: To evaluate the differences in diffusion-weighted imaging (DWI) of the fetal brain between normotensive pregnancies and PE/GH pregnancies, with a focus on PE/GH pregnancies with fetal growth restriction (FGR). STUDY TYPE: Retrospective matched case-control study. POPULATION: 40 singleton pregnancies with PE/GH complicated by FGR, and 3 paired control groups (PE/GH without FGR, normotensive FGR, normotensive pregnancies) (28-38 gestational weeks). FIELD STRENGTH/SEQUENCE: DWI with single-shot echo-planar imaging at 1.5 Tesla. ASSESSMENT: The apparent diffusion coefficient (ADC) values were calculated in the centrum semi-ovale (CSO), parietal white matter (PWM), frontal white matter (FWM), occipital white matter (OWM), temporal white matter (TWM), basal ganglia, thalamus (THAL), pons, and cerebellar hemisphere. STATISTICAL TESTS: Student t test or Wilcoxon matched test was used to reveal the difference of ADC values among the investigated brain regions. A correlation between gestational age (GA) and ADC values was determined by linear regression analysis. RESULTS: Compared with fetuses in PE/GH without FGR and those with normotensive pregnancies, fetuses in the PE/GH with FGR group had significantly lower average ADC measurements of supratentorial regions (1.65 ± 0.09 vs. 1.71 ± 0.10 10-3 mm2 /sec; vs. 1.73 ± 0.11 10-3 mm2 /sec, respectively). Regions of significantly decreased ADC values in the fetal brain included CSO, FWM, PWM, OWM, TWM and THAL in cases of PE/GH with FGR. ADC values from supratentorial regions in PE/GH pregnancies were not significantly correlated with GA (P = 0.12, 0.26); however, this trend was statistically significant in the normotensive groups. DATA CONCLUSION: ADC values may indicate fetal brain developmental alterations in PE/GH with FGR fetuses but more microscopic and morphological studies are necessary to provide additional evidence to offer a different interpretation of this trend in fetal brain. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.

Predictive Value of the Diffusion Magnetic Resonance Imaging Technique for the Postoperative Outcome of Cervical Spondylotic Myelopathy.

BACKGROUND: Diffusion magnetic resonsance imaging (dMRI) can potentially predict the postoperative outcome of cervical spondylotic myelopathy (CSM). PURPOSE: To explore preoperative dMRI parameters to predict the postoperative outcome of CSM through multifactor correlation analysis. STUDY TYPE: Prospective. POPULATION: Post-surgery CSM patients; 102 total, 73 male (52.42 ± 10.60 years old) and 29 female (52.0 ± 11.45 years old). FIELD STRENGTH/SEQUENCE: 3.0 T/Turbo spin echo T1/T2-weighted, T2*-weighted multiecho gradient echo and dMRI. ASSESSMENT: Spinal cord function was evaluated using modified Japanese Orthopedic Association (mJOA) scoring at different time points: preoperative and 3, 6, and 12 months postoperative. Single-factor correlation and t test analyses were conducted based on fractional anisotropy (FA), mean diffusivity, intracellular volume fraction, isotropic volume fraction, orientation division index, increased signal intensity, compression ratio, age, sex, symptom duration and operation method, and multicollinearity was calculated. The linear quantile mixed model (LQMM) and the linear mixed-effects regression model (LMER) were used for multifactor correlation analysis using the combinations of the above variables. STATISTICAL TESTS: Distance correlation, Pearson's correlation, multiscale graph correlation and t tests were used for the single-factor correlation analyses. The variance inflation factor (VIF) was used to calculate multicollinearity. LQMM and LMER were used for multifactor correlation analyses. P < 0.05 was considered statistically significant. RESULTS: The single-factor correlation between all variables and the postoperative mJOA score was weak (all r < 0.3). The linear relationship was stronger than the nonlinear relationship, and there was no significant multicollinearity (VIF = 1.10-1.94). FA values in the LQMM and LMER models had a significant positive correlation with the mJOA score (r = 5.27-6.04), which was stronger than the other variables. DATA CONCLUSION: The FA value based on dMRI significantly positively correlated with CSM patient postoperative outcomes, helping to predict the surgical outcome and formulate a treatment plan before surgery. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

U-fiber diffusion kurtosis and susceptibility characteristics in relapsing-remitting multiple sclerosis may be related to cognitive deficits and neurodegeneration.

OBJECTIVES: To evaluate the diffusion kurtosis and susceptibility change in the U-fiber region of patients with relapsing-remitting multiple sclerosis (pwRRMS) and their correlations with cognitive status and degeneration. MATERIALS AND METHODS: Mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), kurtosis fractional anisotropy (KFA), and the mean relative quantitative susceptibility mapping (mrQSM) values in the U-fiber region were compared between 49 pwRRMS and 48 healthy controls (HCs). The U-fiber were divided into upper and deeper groups based on the location. The whole brain volume, gray and white matter volume, and cortical thickness were obtained. The correlations between the mrQSM values, DKI-derived metrics in the U-fiber region and clinical scale scores, brain morphologic parameters were further investigated. RESULTS: The decreased MK, AK, RK, KFA, and increased mrQSM values in U-fiber lesions (p < 0.001, FDR corrected), decreased RK, KFA, and increased mrQSM values in U-fiber non-lesions (p = 0.034, p < 0.001, p < 0.001, FDR corrected) were found in pwRRMS. There were differences in DKI-derived metrics and susceptibility values between the upper U-fiber region and the deeper one for U-fiber non-lesion areas of pwRRMS and HCs (p < 0.05), but not for U-fiber lesions in DKI-derived metrics. The DKI-derived metrics and susceptibility values were widely related with cognitive tests and brain atrophy. CONCLUSION: RRMS patients show abnormal diffusion kurtosis and susceptibility characteristics in the U-fiber region, and these underlying tissue abnormalities are correlated with cognitive deficits and degeneration. CLINICAL RELEVANCE STATEMENT: The macroscopic and microscopic tissue damages of U-fiber help to identify cognitive impairment and brain atrophy in multiple sclerosis and provide underlying pathophysiological mechanism. KEY POINTS: • Diffusion kurtosis and susceptibility changes are present in the U-fiber region of multiple sclerosis. • There are gradients in diffusion kurtosis and susceptibility characteristics in the U-fiber region. • Tissue damages in the U-fiber region are correlated with cognitive impairment and brain atrophy.

T2* cartilage mapping in early axial spondyloarthritis: diagnostic accuracy and correlation with clinical characteristics, sacroiliitis MRI scorings, and diffusion metrics.

PURPOSE: To determine the performance of T2* cartilage mapping in diagnosing and assessing disease activity in early axial spondyloarthritis (axSpA), and to investigate the interaction of cartilage damage with clinical characteristics, sacroiliitis MRI scorings, and diffusion metrics. MATERIALS AND METHODS: This prospective study included 83 axSpA patients and 37 no-axSpA patients. Clinical characteristics, the Assessment of SpondyloArthritis International Society-defined active sacroiliitis on MRI, and T2* SIJs values were recorded. In axSpA, disease activity was evaluated using the ankylosing spondylitis disease activity score-C-reactive protein; active sacroiliitis was evaluated using Spondyloarthritis Research Consortium of Canada, intravoxel incoherent motion, and diffusion kurtosis imaging; chronic sacroiliitis was assessed using composite structural damage score (CSDS) and structural score fat. Mann-Whitney U-test, Kruskal-Wallis test with false discovery rate (FDR), ROC curve, and linear regression were used for statistical analysis. RESULTS: AxSpA patients had significantly higher T2*SIJs values than no-axSpA patients. (22.86 ± 2.42 ms vs 20.36 ± 1.30 ms, p < 0.001). The combination of T2*SIJs values and active sacroiliitis on MRI had the highest AUC for identifying axSpA. T2*SIJs values were significantly different between the inactive and very high, moderate and very high, high and very high, as well as inactive and high disease activity groups (all pFDR < 0.05). Dk (ß = 0.48) and CSDS (ß = 0.48) were independently associated with T2*SIJs values. CONCLUSION: T2* values may be a promising biomarker for diagnosing and differentiating disease activity in early axSpA. Both acute and chronic sacroiliitis influence cartilage properties. CLINICAL RELEVANCE STATEMENT: Sacroiliac joint cartilage abnormalities can be quantified with T2* relaxation time and allow better characterization of early axSpA. KEY POINTS: T2* mapping may have value in evaluating axSpA. The combination of T2* values and active sacroiliitis on MRI enhances diagnostic performance for axSpA. Abnormalities measured with T2* values correlate with disease activity, acute sacroiliitis, and degree of structural damage.

Discrimination between human epidermal growth factor receptor 2 (HER2)-low-expressing and HER2-overexpressing breast cancers: a comparative study of four MRI diffusion models.

OBJECTIVES: To determine the value of conventional DWI, continuous-time random walk (CTRW), fractional order calculus (FROC), and stretched exponential model (SEM) in discriminating human epidermal growth factor receptor 2 (HER2) status of breast cancer (BC). METHODS: This prospective study included 158 women who underwent DWI, CTRW, FROC, and SEM and were pathologically categorized into the HER2-zero-expressing group (n = 10), HER2-low-expressing group (n = 86), and HER2-overexpressing group (n = 62). Nine diffusion parameters, namely ADC, αCTRW, ßCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM of the primary tumor, were derived from four diffusion models. These diffusion metrics and clinicopathologic features were compared between groups. Logistic regression was used to determine the optimal diffusion metrics and clinicopathologic variables for classifying the HER2-expressing statuses. Receiver operating characteristic (ROC) curves were used to evaluate their discriminative ability. RESULTS: The estrogen receptor (ER) status, progesterone receptor (PR) status, and tumor size differed between HER2-low-expressing and HER2-overexpressing groups (p < 0.001 to p = 0.009). The αCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM were significantly lower in HER2-low-expressing BCs than those in HER2-overexpressing BCs (p < 0.001 to p = 0.01). Further multivariable logistic regression analysis showed that the αCTRW was the single best discriminative metric, with an area under the curve (AUC) being higher than that of ADC (0.802 vs. 0.610, p < 0.05); the addition of ER status, PR status, and tumor size to the αCTRW improved the AUC to 0.877. CONCLUSIONS: The αCTRW could help discriminate the HER2-low-expressing and HER2-overexpressing BCs. CLINICAL RELEVANCE STATEMENT: Human epidermal growth factor receptor 2 (HER2)-low-expressing breast cancer (BC) might also benefit from the HER2-targeted therapy. Prediction of HER2-low-expressing BC or HER2-overexpressing BC is crucial for appropriate management. Advanced continuous-time random walk diffusion MRI offers a solution to this clinical issue. KEY POINTS: • Human epidermal receptor 2 (HER2)-low-expressing BC had lower αCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM values compared with HER2-overexpressing breast cancer. • The αCTRW was the single best diffusion metric (AUC = 0.802) for discrimination between the HER2-low-expressing and HER2-overexpressing breast cancers. • The addition of αCTRW to the clinicopathologic features (estrogen receptor status, progesterone receptor status, and tumor size) further improved the discriminative ability.

Detection of recurrent high-grade glioma using microstructure characteristics of distinct metabolic compartments in a multimodal and integrative 18F-FET PET/fast-DKI approach.

OBJECTIVES: Differentiation between high-grade glioma (HGG) and post-treatment-related effects (PTRE) is challenging, but advanced imaging techniques were shown to provide benefit. We aim to investigate microstructure characteristics of metabolic compartments identified from amino acid PET and to evaluate the diagnostic potential of this multimodal and integrative O-(2-18F-fluoroethyl)-L-tyrosine-(FET)-PET and fast diffusion kurtosis imaging (DKI) approach for the detection of recurrence and IDH genotyping. METHODS: Fifty-nine participants with neuropathologically confirmed recurrent HGG (n = 39) or PTRE (n = 20) were investigated using static 18F-FET PET and a fast-DKI variant. PET and advanced diffusion metrics of metabolically defined (80-100% and 60-75% areas of 18F-FET uptake) compartments were assessed. Comparative analysis was performed using Mann-Whitney U tests with Holm-Sídák multiple-comparison test and Wilcoxon signed-rank test. Receiver operating characteristic (ROC) curves, regression, and Spearman's correlation analysis were used for statistical evaluations. RESULTS: Compared to PTRE, recurrent HGG presented increased 18F-FET uptake and diffusivity (MD60), but lower (relative) mean kurtosis tensor (rMKT60) and fractional anisotropy (FA60) (respectively p < .05). Diffusion metrics determined from the metabolic periphery showed improved diagnostic performance - most pronounced for FA60 (AUC = 0.86, p < .001), which presented similar benefit to 18F-FET PET (AUC = 0.86, p < .001) and was negatively correlated with amino acid uptake (rs = - 0.46, p < .001). When PET and DKI metrics were evaluated in a multimodal biparametric approach, TBRmax + FA60 showed highest diagnostic accuracy (AUC = 0.93, p < .001), which improved the detection of relapse compared to PET alone (difference in AUC = 0.069, p = .04). FA60 and MD60 distinguished the IDH genotype in the post-treatment setting. CONCLUSION: Detection of glioma recurrence benefits from a multimodal and integrative PET/DKI approach, which presented significant diagnostic advantage to the assessment based on PET alone. CLINICAL RELEVANCE STATEMENT: A multimodal and integrative 18F-FET PET/fast-DKI approach for the non-invasive microstructural characterization of metabolic compartments provided improved diagnostic capability for differentiation between recurrent glioma and post-treatment-related changes, suggesting a role for the diagnostic workup of patients in post-treatment settings. KEY POINTS: • Multimodal PET/MRI with integrative analysis of 18F-FET PET and fast-DKI presents clinical benefit for the assessment of CNS cancer, particularly for the detection of recurrent high-grade glioma. • Microstructure markers of the metabolic periphery yielded biologically pertinent estimates characterising the tumour microenvironment, and, thereby, presented improved diagnostic accuracy with similar accuracy to amino acid PET. • Combined 18F-FET PET/fast-DKI achieved the best diagnostic performance for detection of high-grade glioma relapse with significant benefit to the assessment based on PET alone.

The value of baseline 18F-sodium fluoride and 18F-choline PET activity for identifying responders to radium-223 treatment in castration-resistant prostate cancer bone metastases.

OBJECTIVES: To investigate whether baseline 18F-sodium fluoride (NaF) and 18F-choline PET activity is associated with metastatic castration-resistant prostate cancer (mCRPC) global and individual bone metastases' DWI MR imaging response to radium-223 treatment. METHODS: Thirty-six bone-only mCRPC patients were prospectively recruited from three centers. Whole-body (WB)-MRI with DWI and 18F-NaF and 18F-choline PET/CT were performed at therapy baseline and 8-week intervals. In each patient, bone disease median global (g)ADC change between baseline and follow-up was calculated. Additionally, up to five bone target lesions per patient were delineated and individual median ADC change recorded. An ADC increase > 30% defined response per-patient and per-lesion. For the same targets, baseline 18F-NaF and 18F-choline PET SUVmax were recorded. Mean SUVmax across patient targets was correlated with gADC change and lesion SUVmax with per-lesion ADC change. RESULTS: A total of 133 lesions in 36 patients (14 responders) were analyzed. 18F-NaF PET per-patient mean SUVmax was significantly higher in responders (median = 56.0 versus 38.7 in non-responders; p = 0.008), with positive correlation between SUVmax and gADC increase (rho = 0.42; p = 0.015). A 48.7 SUVmax threshold identified responders with 77% sensitivity and 75% specificity. Baseline 18F-NaF PET per-lesion SUVmax was higher in responding metastases (median = 51.6 versus 31.8 in non-responding metastases; p = 0.001), with positive correlation between baseline lesion SUVmax and ADC increase (rho = 0.39; p < 0.001). A 36.8 SUVmax threshold yielded 72% sensitivity and 63% specificity. No significant association was found between baseline 18F-choline PET SUVmax and ADC response on a per-patient (p = 0.164) or per-lesion basis (p = 0.921). CONCLUSION: 18F-NaF PET baseline SUVmax of target mCRPC bone disease showed significant association with response to radium-223 defined by ADC change. CLINICAL RELEVANCE STATEMENT: 18F-sodium fluoride PET/CT baseline maximum SUV of castration-resistant prostate cancer bone metastases could be used as a predictive biomarker for response to radium-223 therapy. KEY POINTS: • 18F-sodium fluoride PET baseline SUVmax of castration-resistant prostate cancer bone metastases showed significant association with response to radium-223. • Baseline 18F-sodium fluoride PET can improve patient selection for radium-223 therapy. • Change in whole-body DWI parameters can be used for response correlation with baseline 18F-sodium fluoride PET SUVmax in castration-resistant prostate cancer bone metastases.

Diffusion histogram profiles predict molecular features of grade 4 in histologically lower-grade adult diffuse gliomas following WHO classification 2021.

OBJECTIVES: In the latest World Health Organization classification 2021, grade 4 adult diffuse gliomas can be diagnosed with several molecular features even without histological evidence of necrosis or microvascular proliferation. We aimed to explore whole tumor histogram-derived apparent diffusion coefficient (ADC) histogram profiles for differentiating between the presence (Mol-4) and absence (Mol-2/3) of grade 4 molecular features in histologically lower-grade gliomas. METHODS: Between June 2019 and October 2022, 184 adult patients with diffuse gliomas underwent MRI. After excluding 121 patients, 18 (median age, 64.5 [range, 37-84 years]) Mol-4 and 45 (median 40 [range, 18-73] years) Mol-2/3 patients with histologically lower-grade gliomas were enrolled. Whole tumor volume-of-interest-derived ADC histogram profiles were calculated and compared between the two groups. Stepwise logistic regression analysis with Akaike's information criterion using the ADC histogram profiles with p values < 0.01 and age at diagnosis was used to identify independent variables for predicting the Mol-4 group. RESULTS: The 90th percentile (p < 0.001), median (p < 0.001), mean (p < 0.001), 10th percentile (p = 0.014), and entropy (p < 0.001) of normalized ADC were lower, and kurtosis (p < 0.001) and skewness (p = 0.046) were higher in the Mol-4 group than in the Mol-2/3 group. Multivariate logistic regression analysis revealed that the entropy of normalized ADC and age at diagnosis were independent predictive parameters for the Mol-4 group with an area under the curve of 0.92. CONCLUSION: ADC histogram profiles may be promising preoperative imaging biomarkers to predict molecular grade 4 among histologically lower-grade adult diffuse gliomas. CLINICAL RELEVANCE STATEMENT: This study highlighted the diagnostic usefulness of ADC histogram profiles to differentiate histologically lower grade adult diffuse gliomas with the presence of molecular grade 4 features and those without. KEY POINTS: • ADC histogram profiles to predict molecular CNS WHO grade 4 status among histologically lower-grade adult diffuse gliomas were evaluated. • Entropy of ADC and age were independent predictive parameters for molecular grade 4 status. • ADC histogram analysis is useful for predicting molecular grade 4 among histologically lower-grade gliomas.

Spinal cord perfusion is associated with microstructural damage in cervical spondylotic myelopathy patients who underwent cervical laminoplasty.

OBJECTIVES: To investigate the association between spinal cord perfusion and microstructural damage in CSM patients who underwent cervical laminoplasty using MR dynamic susceptibility contrast (DSC), diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI) techniques. METHODS: A follow-up cohort study was conducted with 53 consecutively recruited CSM patients who had undergone cervical laminoplasty 12-14 months after the surgery from April 2016 to December 2016. Twenty-one aged-matched healthy volunteers were recruited as controls. For each patient, decompressed spinal cord levels were imaged on a 3.0-T MRI scanner by diffusion and DSC sequences to quantify the degrees of microstructural damage and perfusion conditions, respectively. The diffusion data were analyzed by DTI and NODDI models to produce diffusion metrics. Classic indicator dilution model was used to quantify the DSC metrics. Mann-Whitney U test was performed for comparison of diffusion metrics between patients and healthy controls. Pearson correlation was used to explore the associations between the metrics of spinal cord perfusion and microstructural damage. RESULTS: DTI metrics, neurite density, and isotropic volume fraction had significant differences between postoperative patients and healthy controls. Pearson correlation test showed that SCBV was significantly positively correlated with RD, MD, and ODI, and negatively correlated with FA and NDI. SCBF was found to be significantly positively correlated with RD and MD, and negatively correlated with FA. CONCLUSIONS: Increased spinal cord perfusion quantified by DSC is associated with microstructural damage assessed by diffusion MRI in CSM patients who underwent cervical laminoplasty. CLINICAL RELEVANCE STATEMENT: This study found that the spinal cord perfusion is associated with microstructural damage in postoperative cervical spondylotic myelopathy patients, indicating that high perfusion may play a role in the pathophysiological process of cervical spondylotic myelopathy and deserves more attention. KEY POINTS: • Spinal cord microstructural damage can be persistent despite the compression had been relieved 12-14 months after the cervical laminoplasty in cervical spondylotic myelopathy (CSM) patients. • Spinal cord perfusion is associated with microstructural damage in CSM patients after the cervical laminoplasty. • Inflammation in the decompressed spinal cord may be a cause of increased perfusion and is associated with microstructural damage during the recovery period of CSM.

MRI with DWI improves detection of liver metastasis and selection of surgical candidates with pancreatic cancer: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis to evaluate if magnetic resonance imaging (MRI) with diffusion weighted imaging (DWI) adds value compared to contrast-enhanced computed tomography (CECT) alone in the preoperative evaluation of pancreatic cancer. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for relevant published studies through October 2022. Studies met eligibility criteria if they evaluated the per-patient diagnostic performance of MRI with DWI in the preoperative evaluation of newly diagnosed pancreatic cancer compared to CECT. Our primary outcome was the number needed to treat (NNT) to prevent one futile surgery using MRI with DWI, defined as those in which CECT was negative and MRI with DWI was positive for liver metastasis (i.e., surgical intervention in metastatic disease missed by CECT). The secondary outcomes were to determine the diagnostic performance and the NNT of MRI with DWI to change management in pancreatic cancer. RESULTS: Nine studies met the inclusion criteria with a total of 1121 patients, of whom 172 had liver metastasis (15.3%). The proportion of futile surgeries reduced by MRI with DWI was 6.0% (95% CI, 3.0-11.6%), yielding an NNT of 16.6. The proportion of cases that MRI with DWI changed management was 18.1% (95% CI, 9.9-30.7), corresponding to an NNT of 5.5. The per-patient sensitivity and specificity of MRI were 92.4% (95% CI, 87.4-95.6%) and 97.3% (95% CI, 96.0-98.1). CONCLUSION: MRI with DWI may prevent futile surgeries in pancreatic cancer by improving the detection of occult liver metastasis on preoperative CECT with an NNT of 16.6. CLINICAL RELEVANCE STATEMENT: MRI with DWI complements the standard preoperative CECT evaluation for liver metastasis in pancreatic cancer, improving the selection of surgical candidates and preventing unnecessary surgeries. KEY POINTS: • The NNT of MRI with DWI to prevent potential futile surgeries due to occult liver metastasis on CECT, defined as those in which CECT was negative and MRI with DWI was positive for liver metastasis, in patients with pancreatic cancer was 16.6. • The higher performance of MRI with DWI to detect liver metastasis occult on CECT can be attributed to an increased detection of subcentimeter liver metastasis.

Assessment of whole-body MRI including diffusion-weighted sequences in the initial staging of breast cancer patients at high risk of metastases in comparison with PET-CT: a prospective cohort study.

OBJECTIVE: The aim of this study was to assess the diffusion-weighted whole-body-MRI (WBMRI) in the initial staging of breast cancer at high risk of metastases in comparison with positron emission tomography (PET)-CT. METHODS: Forty-five women were prospectively enrolled. The inclusion criteria were female gender, age >18, invasive breast cancer, an initial PET-CT, and a performance status of 0-2. The exclusion criteria were contraindication to WB-MRI and breast cancer recurrence. The primary outcome was the concordance of WB-MRI and PET-CT in the diagnosis of distant metastases, whereas secondary outcomes included their concordance for the primary tumor and regional lymph nodes (LN), as well as the agreement of WB-MRI interpretation between two radiologists. RESULTS: The mean age was 51.2 years with a median size of the primary tumor of 30 mm. Concordance between the two modalities was almost perfect for metastases staging, all sites included (k = 0.862), with excellent interobserver agreement. The accuracy of WB-MRI for detecting regional LN, distant LN, lung, liver, or bone metastases ranged from 91 to 96%. In 2 patients, WB-MRI detected bone metastases that were overlooked by PET-CT. WB-MRI showed a substantial agreement with PET-CT for staging the primary tumor, regional LN status, and stage (k = 0.766, k = 0.756, and k = 0.785, respectively) with a high interobserver agreement. CONCLUSION: WB-MRI including DWI could be a reliable and reproducible examination in the initial staging of breast cancer patients at high risk of metastases, especially for bone metastases and therefore could be used as a surrogate to PET-CT. CLINICAL RELEVANCE STATEMENT: Whole-body-MRI including DWI is a promising technique for detecting metastases in the initial staging of breast cancer at high risk of metastases. KEY POINTS: Whole-body-MRI (WB-MRI) was effective for detecting metastases in the initial staging of 45 breast cancer patients at high risk of metastases in comparison with PET-CT. Concordance between WB-MRI and PET-CT was almost perfect for metastases staging, all sites included, with excellent interobserver agreement. The accuracy of WB-MRI for detecting bone metastases was 92%.

Radiomics analysis from magnetic resonance imaging in predicting the grade of nonfunctioning pancreatic neuroendocrine tumors: a multicenter study.

OBJECTIVES: To explore the potential of radiomics features to predict the histologic grade of nonfunctioning pancreatic neuroendocrine tumor (NF-PNET) patients using non-contrast sequence based on MRI. METHODS: Two hundred twenty-eight patients with NF-PNETs undergoing MRI at 5 centers were retrospectively analyzed. Data from center 1 (n = 115) constituted the training cohort, and data from centers 2-5 (n = 113) constituted the testing cohort. Radiomics features were extracted from T2-weighted images and the apparent diffusion coefficient. The least absolute shrinkage and selection operator was applied to select the most important features and to develop radiomics signatures. The area under receiver operating characteristic curve (AUC) was performed to assess models. RESULTS: Tumor boundary, enhancement homogeneity, and vascular invasion were used to construct the radiological model to stratify NF-PNET patients into grade 1 and 2/3 groups, which yielded AUC of 0.884 and 0.684 in the training and testing groups. A radiomics model including 4 features was constructed, with an AUC of 0.941 and 0.871 in the training and testing cohorts. The fusion model combining the radiomics signature and radiological characteristics showed good performance in the training set (AUC = 0.956) and in the testing set (AUC = 0.864), respectively. CONCLUSION: The developed model that integrates radiomics features with radiological characteristics could be used as a non-invasive, dependable, and accurate tool for the preoperative prediction of grade in NF-PNETs. CLINICAL RELEVANCE STATEMENT: Our study revealed that the fusion model based on a non-contrast MR sequence can be used to predict the histologic grade before operation. The radiomics model may be a new and effective biological marker in NF-PNETs. KEY POINTS: The diagnostic performance of the radiomics model and fusion model was better than that of the model based on clinical information and radiological features in predicting grade 1 and 2/3 of nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs). Good performance of the model in the four external testing cohorts indicated that the radiomics model and fusion model for predicting the grades of NF-PNETs were robust and reliable, indicating the two models could be used in the clinical setting and facilitate the surgeons' decision on risk stratification. The radiomics features were selected from non-contrast T2-weighted images (T2WI) and diffusion-weighted imaging (DWI) sequence, which means that the administration of contrast agent was not needed in grading the NF-PNETs.

Comparison of diffusion-weighted MRI and [18F]FDG PET/MRI for treatment monitoring in pediatric Hodgkin and non-Hodgkin lymphoma.

OBJECTIVE: To compare tumor therapy response assessments with whole-body diffusion-weighted imaging (WB-DWI) and 18F-fluorodeoxyglucose ([18F]FDG) PET/MRI in pediatric patients with Hodgkin lymphoma and non-Hodgkin lymphoma. MATERIALS AND METHODS: In a retrospective, non-randomized single-center study, we reviewed serial simultaneous WB-DWI and [18F]FDG PET/MRI scans of 45 children and young adults (27 males; mean age, 13 years ± 5 [standard deviation]; age range, 1-21 years) with Hodgkin lymphoma (n = 20) and non-Hodgkin lymphoma (n = 25) between February 2018 and October 2022. We measured minimum tumor apparent diffusion coefficient (ADCmin) and maximum standardized uptake value (SUVmax) of up to six target lesions and assessed therapy response according to Lugano criteria and modified criteria for WB-DWI. We evaluated the agreement between WB-DWI- and [18F]FDG PET/MRI-based response classifications with Gwet's agreement coefficient (AC). RESULTS: After induction chemotherapy, 95% (19 of 20) of patients with Hodgkin lymphoma and 72% (18 of 25) of patients with non-Hodgkin lymphoma showed concordant response in tumor metabolism and proton diffusion. We found a high agreement between treatment response assessments on WB-DWI and [18F]FDG PET/MRI (Gwet's AC = 0.94; 95% confidence interval [CI]: 0.82, 1.00) in patients with Hodgkin lymphoma, and a lower agreement for patients with non-Hodgkin lymphoma (Gwet's AC = 0.66; 95% CI: 0.43, 0.90). After completion of therapy, there was an excellent agreement between WB-DWI and [18F]FDG PET/MRI response assessments (Gwet's AC = 0.97; 95% CI: 0.91, 1). CONCLUSION: Therapy response of Hodgkin lymphoma can be evaluated with either [18F]FDG PET or WB-DWI, whereas patients with non-Hodgkin lymphoma may benefit from a combined approach. CLINICAL RELEVANCE STATEMENT: Hodgkin lymphoma and non-Hodgkin lymphoma exhibit different patterns of tumor response to induction chemotherapy on diffusion-weighted MRI and PET/MRI. KEY POINTS: • Diffusion-weighted imaging has been proposed as an alternative imaging to assess tumor response without ionizing radiation. • After induction therapy, whole-body diffusion-weighted imaging and PET/MRI revealed a higher agreement in patients with Hodgkin lymphoma than in those with non-Hodgkin lymphoma. • At the end of therapy, whole-body diffusion-weighted imaging and PET/MRI revealed an excellent agreement for overall tumor therapy responses for all lymphoma types.