Motion guidance lines for robust data consistency-based retrospective motion correction in 2D and 3D MRI.

PURPOSE: To develop a robust retrospective motion-correction technique based on repeating k-space guidance lines for improving motion correction in Cartesian 2D and 3D brain MRI. METHODS: The motion guidance lines are inserted into the standard sequence orderings for 2D turbo spin echo and 3D MPRAGE to inform a data consistency-based motion estimation and reconstruction, which can be guided by a low-resolution scout. The extremely limited number of required guidance lines are repeated during each echo train and discarded in the final image reconstruction. Thus, integration within a standard k-space acquisition ordering ensures the expected image quality/contrast and motion sensitivity of that sequence. RESULTS: Through simulation and in vivo 2D multislice and 3D motion experiments, we demonstrate that respectively 2 or 4 optimized motion guidance lines per shot enables accurate motion estimation and correction. Clinically acceptable reconstruction times are achieved through fully separable on-the-fly motion optimizations (˜1 s/shot) using standard scanner GPU hardware. CONCLUSION: The addition of guidance lines to scout accelerated motion estimation facilitates robust retrospective motion correction that can be effectively introduced without perturbing standard clinical protocols and workflows.

Validation of a highly accelerated post-contrast wave-controlled aliasing in parallel imaging (CAIPI) 3D-T1 MPRAGE compared to standard 3D-T1 MPRAGE for detection of intracranial enhancing lesions on 3-T MRI.

OBJECTIVES: High-resolution post-contrast T1-weighted imaging is a workhorse sequence in the evaluation of neurological disorders. The T1-MPRAGE sequence has been widely adopted for the visualization of enhancing pathology in the brain. However, this three-dimensional (3D) acquisition is lengthy and prone to motion artifact, which often compromises diagnostic quality. The goal of this study was to compare a highly accelerated wave-controlled aliasing in parallel imaging (CAIPI) post-contrast 3D T1-MPRAGE sequence (Wave-T1-MPRAGE) with the standard 3D T1-MPRAGE sequence for visualizing enhancing lesions in brain imaging at 3 T. METHODS: This study included 80 patients undergoing contrast-enhanced brain MRI. The participants were scanned with a standard post-contrast T1-MPRAGE sequence (acceleration factor [R] = 2 using GRAPPA parallel imaging technique, acquisition time [TA] = 5 min 18 s) and a prototype post-contrast Wave-T1-MPRAGE sequence (R = 4, TA = 2 min 32 s). Two neuroradiologists performed a head-to-head evaluation of both sequences and rated the visualization of enhancement, sharpness, noise, motion artifacts, and overall diagnostic quality. A 15% noninferiority margin was used to test whether post-contrast Wave-T1-MPRAGE was noninferior to standard T1-MPRAGE. Inter-rater and intra-rater agreement were calculated. Quantitative assessment of CNR/SNR was performed. RESULTS: Wave-T1-MPRAGE was noninferior to standard T1-MPRAGE for delineating enhancing lesions with unanimous agreement in all cases between raters. Wave-T1-MPRAGE was noninferior in the perception of noise (p < 0.001), motion artifact (p < 0.001), and overall diagnostic quality (p < 0.001). CONCLUSION: High-accelerated post-contrast Wave-T1-MPRAGE enabled a two-fold reduction in acquisition time compared to the standard sequence with comparable performance for visualization of enhancing pathology and equivalent perception of noise, motion artifacts and overall diagnostic quality without loss of clinically important information. KEY POINTS: • Post-contrast wave-controlled aliasing in parallel imaging (CAIPI) T1-MPRAGE accelerated the acquisition of three-dimensional (3D) high-resolution post-contrast images by more than two-fold. • Post-contrast Wave-T1-MPRAGE was noninferior to standard T1-MPRAGE with unanimous agreement between reviewers (100% in 80 cases) for the visualization of intracranial enhancing lesions. • Wave-T1-MPRAGE was equivalent to the standard sequence in the perception of noise in 94% (75 of 80) of cases and was preferred in 16% (13 of 80) of cases for decreased motion artifact.

Scout accelerated motion estimation and reduction (SAMER).

PURPOSE: To demonstrate a navigator/tracking-free retrospective motion estimation technique that facilitates clinically acceptable reconstruction time. METHODS: Scout accelerated motion estimation and reduction (SAMER) uses a single 3-5 s, low-resolution scout scan and a novel sequence reordering to independently determine motion states by minimizing the data-consistency error in a SENSE plus motion forward model. This eliminates time-consuming alternating optimization as no updates to the imaging volume are required during the motion estimation. The SAMER approach was assessed quantitatively through extensive simulation and was evaluated in vivo across multiple motion scenarios and clinical imaging contrasts. Finally, SAMER was synergistically combined with advanced encoding (Wave-CAIPI) to facilitate rapid motion-free imaging. RESULTS: The highly accelerated scout provided sufficient information to achieve accurate motion trajectory estimation (accuracy ~0.2 mm or degrees). The novel sequence reordering improved the stability of the motion parameter estimation and image reconstruction while preserving the clinical imaging contrast. Clinically acceptable computation times for the motion estimation (~4 s/shot) are demonstrated through a fully separable (non-alternating) motion search across the shots. Substantial artifact reduction was demonstrated in vivo as well as corresponding improvement in the quantitative error metric. Finally, the extension of SAMER to Wave-encoding enabled rapid high-quality imaging at up to R = 9-fold acceleration. CONCLUSION: SAMER significantly improved the computational scalability for retrospective motion estimation and correction.

Optimization of magnetization transfer contrast for EPI FLAIR brain imaging.

PURPOSE: To evaluate the impact of magnetization transfer (MT) on brain tissue contrast in turbo-spin-echo (TSE) and EPI fluid-attenuated inversion recovery (FLAIR) images, and to optimize an MT-prepared EPI FLAIR pulse sequence to match the tissue contrast of a clinical reference TSE FLAIR protocol. METHODS: Five healthy volunteers underwent 3T brain MRI, including single slice TSE FLAIR, multi-slice TSE FLAIR, EPI FLAIR without MT-preparation, and MT-prepared EPI FLAIR with variations of the MT-preparation parameters, including number of preparation pulses, pulse amplitude, and resonance offset. Automated co-registration and gray matter (GM) versus white matter (WM) segmentation was performed using a T1-MPRAGE acquisition, and the GM versus WM signal intensity ratio (contrast ratio) was calculated for each FLAIR acquisition. RESULTS: Without MT preparation, EPI FLAIR showed poor tissue contrast (contrast ratio = 0.98), as did single slice TSE FLAIR. Multi-slice TSE FLAIR provided high tissue contrast (contrast ratio = 1.14). MT-prepared EPI FLAIR closely approximated the contrast of the multi-slice TSE FLAIR images for two combinations of the MT-preparation parameters (contrast ratio = 1.14). Optimized MT-prepared EPI FLAIR provided a 50% reduction in scan time compared to the reference TSE FLAIR acquisition. CONCLUSION: Optimized MT-prepared EPI FLAIR provides comparable brain tissue contrast to the multi-slice TSE FLAIR images used in clinical practice.

An artificial intelligence-accelerated 2-minute multi-shot echo planar imaging protocol for comprehensive high-quality clinical brain imaging.

PURPOSE: We introduce and validate an artificial intelligence (AI)-accelerated multi-shot echo-planar imaging (msEPI)-based method that provides T1w, T2w, T2∗ , T2-FLAIR, and DWI images with high SNR, high tissue contrast, low specific absorption rates (SAR), and minimal distortion in 2 minutes. METHODS: The rapid imaging technique combines a novel machine learning (ML) scheme to limit g-factor noise amplification and improve SNR, a magnetization transfer preparation module to provide clinically desirable contrast, and high per-shot EPI undersampling factors to reduce distortion. The ML training and image reconstruction incorporates a tunable parameter for controlling the level of denoising/smoothness. The performance of the reconstruction method is evaluated across various acceleration factors, contrasts, and SNR conditions. The 2-minute protocol is directly compared to a 10-minute clinical reference protocol through deployment in a clinical setting, where five representative cases with pathology are examined. RESULTS: Optimization of custom msEPI sequences and protocols was performed to balance acquisition efficiency and image quality compared to the five-fold longer clinical reference. Training data from 16 healthy subjects across multiple contrasts and orientations were used to produce ML networks at various acceleration levels. The flexibility of the ML reconstruction was demonstrated across SNR levels, and an optimized regularization was determined through radiological review. Network generalization toward novel pathology, unobserved during training, was illustrated in five clinical case studies with clinical reference images provided for comparison. CONCLUSION: The rapid 2-minute msEPI-based protocol with tunable ML reconstruction allows for advantageous trade-offs between acquisition speed, SNR, and tissue contrast when compared to the five-fold slower standard clinical reference exam.

Clinical validation of Wave-CAIPI susceptibility-weighted imaging for routine brain MRI at 1.5 T.

OBJECTIVES: Wave-CAIPI (Controlled Aliasing in Parallel Imaging) enables dramatic reduction in acquisition time of 3D MRI sequences such as 3D susceptibility-weighted imaging (SWI) but has not been clinically evaluated at 1.5 T. We sought to compare highly accelerated Wave-CAIPI SWI (Wave-SWI) with two alternative standard sequences, conventional three-dimensional SWI and two-dimensional T2*-weighted Gradient-Echo (T2*w-GRE), in patients undergoing routine brain MRI at 1.5 T. METHODS: In this study, 172 patients undergoing 1.5 T brain MRI were scanned with a more commonly used susceptibility sequence (standard SWI or T2*w-GRE) and a highly accelerated Wave-SWI sequence. Two radiologists blinded to the acquisition technique scored each sequence for visualization of pathology, motion and signal dropout artifacts, image noise, visualization of normal anatomy (vessels and basal ganglia mineralization), and overall diagnostic quality. Superiority testing was performed to compare Wave-SWI to T2*w-GRE, and non-inferiority testing with 15% margin was performed to compare Wave-SWI to standard SWI. RESULTS: Wave-SWI performed superior in terms of visualization of pathology, signal dropout artifacts, visualization of normal anatomy, and overall image quality when compared to T2*w-GRE (all p < 0.001). Wave-SWI was non-inferior to standard SWI for visualization of normal anatomy and pathology, signal dropout artifacts, and overall image quality (all p < 0.001). Wave-SWI was superior to standard SWI for motion artifact (p < 0.001), while both conventional susceptibility sequences were superior to Wave-SWI for image noise (p < 0.001). CONCLUSIONS: Wave-SWI can be performed in a 1.5 T clinical setting with robust performance and preservation of diagnostic quality. KEY POINTS: • Wave-SWI accelerated the acquisition of 3D high-resolution susceptibility images in 70% of the acquisition time of the conventional T2*GRE. • Wave-SWI performed superior to T2*w-GRE for visualization of pathology, signal dropout artifacts, and overall diagnostic image quality. • Wave-SWI was noninferior to standard SWI for visualization of normal anatomy and pathology, signal dropout artifacts, and overall diagnostic image quality.

Evaluation of highly accelerated wave controlled aliasing in parallel imaging (Wave-CAIPI) susceptibility-weighted imaging in the non-sedated pediatric setting: a pilot study.

BACKGROUND: Susceptibility-weighted imaging (SWI) is highly sensitive for intracranial hemorrhagic and mineralized lesions but is associated with long scan times. Wave controlled aliasing in parallel imaging (Wave-CAIPI) enables greater acceleration factors and might facilitate broader application of SWI, especially in motion-prone populations. OBJECTIVE: To compare highly accelerated Wave-CAIPI SWI to standard SWI in the non-sedated pediatric outpatient setting, with respect to the following variables: estimated scan time, image noise, artifacts, visualization of normal anatomy and visualization of pathology. MATERIALS AND METHODS: Twenty-eight children (11 girls, 17 boys; mean age ± standard deviation [SD] = 128.3±62 months) underwent 3-tesla (T) brain MRI, including standard three-dimensional (3-D) SWI sequence followed by a highly accelerated Wave-CAIPI SWI sequence for each subject. We rated all studies using a predefined 5-point scale and used the Wilcoxon signed rank test to assess the difference for each variable between sequences. RESULTS: Wave-CAIPI SWI provided a 78% and 67% reduction in estimated scan time using the 32- and 20-channel coils, respectively, corresponding to estimated scan time reductions of 3.5 min and 3 min, respectively. All 28 children were imaged without anesthesia. Inter-reader agreement ranged from fair to substantial (k=0.67 for evaluation of pathology, 0.55 for anatomical contrast, 0.3 for central noise, and 0.71 for artifacts). Image noise was rated higher in the central brain with wave SWI (P<0.01), but not in the peripheral brain. There was no significant difference in the visualization of normal anatomical structures and visualization of pathology between the standard and wave SWI sequences (P=0.77 and P=0.79, respectively). CONCLUSION: Highly accelerated Wave-CAIPI SWI of the brain can provide similar image quality to standard SWI, with estimated scan time reduction of 3-3.5 min depending on the radiofrequency coil used, with fewer motion artifacts, at a cost of mild but perceptibly increased noise in the central brain.

Joint super-resolution and synthesis of 1 mm isotropic MP-RAGE volumes from clinical MRI exams with scans of different orientation, resolution and contrast.

Most existing algorithms for automatic 3D morphometry of human brain MRI scans are designed for data with near-isotropic voxels at approximately 1 mm resolution, and frequently have contrast constraints as well-typically requiring T1-weighted images (e.g., MP-RAGE scans). This limitation prevents the analysis of millions of MRI scans acquired with large inter-slice spacing in clinical settings every year. In turn, the inability to quantitatively analyze these scans hinders the adoption of quantitative neuro imaging in healthcare, and also precludes research studies that could attain huge sample sizes and hence greatly improve our understanding of the human brain. Recent advances in convolutional neural networks (CNNs) are producing outstanding results in super-resolution and contrast synthesis of MRI. However, these approaches are very sensitive to the specific combination of contrast, resolution and orientation of the input images, and thus do not generalize to diverse clinical acquisition protocols - even within sites. In this article, we present SynthSR, a method to train a CNN that receives one or more scans with spaced slices, acquired with different contrast, resolution and orientation, and produces an isotropic scan of canonical contrast (typically a 1 mm MP-RAGE). The presented method does not require any preprocessing, beyond rigid coregistration of the input scans. Crucially, SynthSR trains on synthetic input images generated from 3D segmentations, and can thus be used to train CNNs for any combination of contrasts, resolutions and orientations without high-resolution real images of the input contrasts. We test the images generated with SynthSR in an array of common downstream analyses, and show that they can be reliably used for subcortical segmentation and volumetry, image registration (e.g., for tensor-based morphometry), and, if some image quality requirements are met, even cortical thickness morphometry. The source code is publicly available at https://github.com/BBillot/SynthSR.

Platelet bound complement split product (PC4d) is a marker of platelet activation and arterial vascular events in Systemic Lupus Erythematosus.

Platelet-bound complement activation products (PC4d) are associated with thrombosis in Systemic Lupus Erythematosus (SLE). This study investigated the effect of PC4d on platelet function, as a mechanistic link to arterial thrombosis. In a cohort of 150 SLE patients, 13 events had occurred within five years of enrollment. Patients with arterial events had higher PC4d levels (13.6 [4.4-24.0] vs. 4.0 [2.5-8.3] net MFI), with PC4d 10 being the optimal cutoff for event detection. The association of arterial events with PC4d remained significant after adjusting for antiphospholipid status, smoking, and prednisone use (p = 0.045). PC4d levels correlated with lower platelet counts (r = -0.26, p = 0.002), larger platelet volumes (r = 0.22, p = 0.009) and increased platelet aggregation: the adenosine diphosphate (ADP) concentration to achieve 50% maximal aggregation (EC50) was lower in patients with PC4d 10 compared with PC4d < 10 (1.6 vs. 3.7, p = 0.038, respectively). These results suggest that PC4d may be a mechanistic marker for vascular disease in SLE.

Predictors of Anesthetic Exposure in Pediatric MRI.

BACKGROUND. Anesthetic exposure in children may impact long-term neurocognitive outcomes. Therefore, minimizing pediatric MRI scan time in children under anesthesia and the associated anesthetic exposure is necessary. OBJECTIVE. The purpose of this study was to evaluate pediatric MRI scan time as a predictor of total propofol dose, considering imaging and clinical characteristics as covariates. METHODS. Electronic health records were retrospectively searched to identify MRI examinations performed from 2016 to 2019 in patients 0-18 years old who received propofol anesthetic. Brain; brain and spine; brain and abdomen; and brain, head, and neck MRI examinations were included. Demographic, clinical, and imaging data were extracted for each examination, including anesthesia maintenance phase time, MRI scan time, and normalized propofol dose. MRI scan time and propofol dose were compared between groups using a t test. A multiple linear regression with backward selection (threshold, p < .05) was used to evaluate MRI scan time as a predictor of total propofol dose, adjusting for sex, age, time between scan and study end, body part, American Society of Anesthesiologists (ASA) classification, diagnosis, magnet strength, and IV contrast medium administration as covariates. RESULTS. A total of 501 examinations performed in 426 patients (172 girls, 254 boys; mean age, 6.55 ± 4.59 [SD] years) were included. Single body part examinations were shorter than multiple body part examinations (mean, 52.7 ± 18.4 vs 89.3 ± 26.4 minutes) and required less propofol (mean, 17.7 ± 5.7 vs 26.1 ± 7.7 mg/kg; all p < .001). Among single body part examinations, a higher ASA classification, oncologic diagnosis, 1.5-T magnet, and IV contrast medium administration were associated with longer MRI scan times (all p ≤ .009) and higher propofol exposure (all p ≤ .005). In multivariable analysis, greater propofol exposure was predicted by MRI scan time (mean dose per minute of examination, 0.178 mg/kg; 95% CI, 0.155-0.200; p < .001), multiple body part examination (p = .04), and IV contrast medium administration (p = .048); lower exposure was predicted by 3-T magnet (p = .04). CONCLUSION. Anesthetic exposure during pediatric MRI can be quantified and predicted based on imaging and clinical variables. CLINICAL IMPACT. This study serves as a valuable baseline for future efforts to reduce anesthetic doses and scan times in pediatric MRI.

Comparison of ultrafast wave-controlled aliasing in parallel imaging (CAIPI) magnetization-prepared rapid acquisition gradient echo (MP-RAGE) and standard MP-RAGE in non-sedated children: initial clinical experience.

BACKGROUND: Fast magnetic resonance imaging (MRI) sequences are advantageous in pediatric imaging as they can lessen child discomfort, decrease motion artifact and improve scanner availability. OBJECTIVE: To evaluate the feasibility of an ultrafast wave-CAIPI (controlled aliasing in parallel imaging) MP-RAGE (magnetization-prepared rapid gradient echo) sequence for brain imaging of awake pediatric patients. MATERIALS AND METHODS: Each MRI included a standard MP-RAGE sequence and an ultrafast wave-MP-RAGE sequence. Two neuroradiologists evaluated both sequences in terms of artifacts, noise, anatomical contrast and pathological contrast. A predefined 5-point scale was used by two independent pediatric neuroradiologists. A Wilcoxon signed-rank test was used to evaluate the difference between sequences for each variable. RESULTS: Twenty-four patients (14 males; mean age: 11.5±4.5 years, range: 1 month to 17.8 years) were included. Wave-CAIPI MP-RAGE provided a 77% reduction in scan time using a 32-channel coil and a 70% reduction using a 20-channel coil. Visualization of the pathology, artifacts and pathological enhancement (including parenchymal, leptomeningeal and dural enhancement) was not significantly different between standard MP-RAGE and wave-CAIPI MP-RAGE (all P>0.05). For central (P<0.001) and peripheral (P<0.001) noise, and the evaluation of the anatomical structures (P<0.001), the observers favored standard MP-RAGE over wave-CAIPI MP-RAGE. CONCLUSION: Ultrafast brain imaging with wave-CAIPI MP-RAGE is feasible in awake pediatric patients, providing a substantial reduction in scan time at a cost of subjectively increased image noise.

Highly-accelerated volumetric brain examination using optimized wave-CAIPI encoding.

BACKGROUND: Rapid volumetric imaging protocols could better utilize limited scanner resources. PURPOSE: To develop and validate an optimized 6-minute high-resolution volumetric brain MRI examination using Wave-CAIPI encoding. STUDY TYPE: Prospective. POPULATION/SUBJECTS: Ten healthy subjects and 20 patients with a variety of intracranial pathologies. FIELD STRENGTH/SEQUENCE: At 3 T, MPRAGE, T2 -weighted SPACE, SPACE FLAIR, and SWI were acquired at 9-fold acceleration using Wave-CAIPI and for comparison at 2-4-fold acceleration using conventional GRAPPA. ASSESSMENT: Extensive simulations were performed to optimize the Wave-CAIPI protocol and minimize both g-factor noise amplification and potential T1 /T2 blurring artifacts. Moreover, refinements in the autocalibrated reconstruction of Wave-CAIPI were developed to ensure high-quality reconstructions in the presence of gradient imperfections. In a randomized and blinded fashion, three neuroradiologists assessed the diagnostic quality of the optimized 6-minute Wave-CAIPI exam and compared it to the roughly 3× slower GRAPPA accelerated protocol using both an individual and head-to-head analysis. STATISTICAL TEST: A noninferiority test was used to test whether the diagnostic quality of Wave-CAIPI was noninferior to the GRAPPA acquisition, with a 15% noninferiority margin. RESULTS: Among all sequences, Wave-CAIPI achieved negligible g-factor noise amplification (gavg ≤ 1.04) and burring artifacts from T1 /T2 relaxation. Improvements of our autocalibration approach for gradient imperfections enabled increased robustness to gradient mixing imperfections in tilted-field of view (FOV) prescriptions as well as variations in gradient and analog-to-digital converter (ADC) sampling rates. In the clinical evaluation, Wave-CAIPI achieved similar mean scores when compared with GRAPPA (MPRAGE: ØW = 4.03, ØG = 3.97; T2 w SPACE: ØW = 4.00, ØG = 4.00; SPACE FLAIR: ØW = 3.97, ØG = 3.97; SWI: ØW = 3.93, ØG = 3.83) and was statistically noninferior (N = 30, P < 0.05 for all sequences). DATA CONCLUSION: The proposed volumetric brain exam retained comparable image quality when compared with the much longer conventional protocol. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:961-974.

Polycystic Kidney Disease without an Apparent Family History.

The absence of a positive family history (PFH) in 10%-25% of patients poses a diagnostic challenge for autosomal dominant polycystic kidney disease (ADPKD). In the Toronto Genetic Epidemiology Study of Polycystic Kidney Disease, 210 affected probands underwent renal function testing, abdominal imaging, and comprehensive PKD1 and PKD2 mutation screening. From this cohort, we reviewed all patients with and without an apparent family history, examined their parental medical records, and performed renal imaging in all available parents of unknown disease status. Subsequent reclassification of 209 analyzed patients revealed 72.2% (151 of 209) with a PFH, 15.3% (32 of 209) with de novo disease, 10.5% (22 of 209) with an indeterminate family history, and 1.9% (four of 209) with PFH in retrospect. Among the patients with de novo cases, we found two families with germline mosaicism and one family with somatic mosaicism. Additionally, analysis of renal imaging revealed that 16.3% (34 of 209) of patients displayed atypical PKD, most of which followed one of three patterns: asymmetric or focal PKD with PFH and an identified PKD1 or PKD2 mutation (15 of 34), asymmetric and de novo PKD with proven or suspected somatic mosaicism (seven of 34), or focal PKD without any identifiable PKD1 or PKD2 mutation (eight of 34). In conclusion, PKD without an apparent family history may be due to de novo disease, missing parental medical records, germline or somatic mosaicism, or mild disease from hypomorphic PKD1 and PKD2 mutations. Furthermore, mutations of a newly identified gene for ADPKD, GANAB, and somatic mosaicism need to be considered in the mutation-negative patients with focal disease.

Development of White Matter Hyperintensity Is Preceded by Reduced Cerebrovascular Reactivity.

OBJECTIVE: White matter hyperintensities (WMH) observed on neuroimaging of elderly individuals are associated with cognitive decline and disability. However, the pathogenesis of WMH remains poorly understood. We observed that regions of reduced cerebrovascular reactivity (CVR) in the white matter of young individuals correspond to the regions most susceptible to WMH in the elderly. This finding prompted us to consider that reduced CVR may play a role in the pathogenesis of WMH. We hypothesized that reduced CVR precedes development of WMH. METHODS: We examined 45 subjects (age range = 50-91 years; 25 males) with moderate-severe WMH, and measured their baseline CVR using the blood oxygen level-dependent magnetic resonance imaging signal response to a standardized step change in the end-tidal partial pressure of carbon dioxide. Diffusion tensor imaging and transverse relaxation time (T2) relaxometry were performed at baseline and 1-year follow-up, with automated coregistration between time points. Baseline fractional anisotropy (FA), mean diffusivity (MD), T2, and CVR were measured in areas that progressed from normal-appearing white matter (NAWM) to WMH over the 1-year period. RESULTS: CVR and FA values in baseline NAWM that progressed to WMH were lower by mean (standard deviation) = 26.5% (23.2%) and 11.0% (7.2%), respectively, compared to the contralateral homologous NAWM that did not progress (p < 0.001). T2 and MD were higher by 8.7% (7.9%) and 17.0% (8.5%), respectively, compared to the contralateral homologous NAWM (p < 0.001). INTERPRETATION: Areas of reduced CVR precede the progression from NAWM to WMH, suggesting that hemodynamic impairment may contribute to the pathogenesis and progression of age-related white matter disease. Ann Neurol 2016;80:277-285.

Differentiating radiation necrosis from tumor progression in brain metastases treated with stereotactic radiotherapy: utility of intravoxel incoherent motion perfusion MRI and correlation with histopathology.

Radiation necrosis is a serious potential adverse event of stereotactic radiosurgery that cannot be reliably differentiated from recurrent tumor using conventional imaging techniques. Intravoxel incoherent motion (IVIM) is a magnetic resonance imaging (MRI) based method that uses a diffusion-weighted sequence to estimate quantitative perfusion and diffusion parameters. This study evaluated the IVIM-derived apparent diffusion coefficient (ADC) and perfusion fraction (f), and compared the results to the gold standard histopathological-defined outcomes of radiation necrosis or recurrent tumor. Nine patients with ten lesions were included in this study; all lesions exhibited radiographic progression after stereotactic radiosurgery for brain metastases that subsequently underwent surgical resection due to uncertainty regarding the presence of radiation necrosis versus recurrent tumor. Pre-surgical IVIM was performed to obtain f and ADC values and the results were compared to histopathology. Five lesions exhibited pathological radiation necrosis and five had predominantly recurrent tumor. The IVIM perfusion fraction reliably differentiated tumor recurrence from radiation necrosis (fmean = 10.1 ± 0.7 vs. 8.3 ± 1.2, p = 0.02; cutoff value of 9.0 yielding a sensitivity/specificity of 100%/80%) while the ADC did not distinguish between the two (ADCmean = 1.1 ± 0.2 vs. 1.2 ± 0.4, p = 0.6). IVIM shows promise in differentiating recurrent tumor from radiation necrosis for brain metastases treated with radiosurgery, but needs to be validated in a larger cohort.

Temporal evolution of perfusion parameters in brain metastases treated with stereotactic radiosurgery: comparison of intravoxel incoherent motion and dynamic contrast enhanced MRI.

Intravoxel incoherent motion (IVIM) is a magnetic resonance imaging (MRI) technique that is seeing increasing use in neuro-oncology and offers an alternative to contrast-enhanced perfusion techniques for evaluation of tumor blood volume after stereotactic radiosurgery (SRS). To date, IVIM has not been validated against contrast enhanced techniques for brain metastases after SRS. In the present study, we measure blood volume for 20 brain metastases (15 patients) at baseline, 1 week and 1 month after SRS using IVIM and dynamic contrast enhanced (DCE)-MRI. Correlation between blood volume measurements made with IVIM and DCE-MRI show poor correlation at baseline, 1 week, and 1 month post SRS (r = 0.33, 0.14 and 0.30 respectively). At 1 week after treatment, no significant change in tumor blood volume was found using IVIM or DCE-MRI (p = 0.81 and 0.41 respectively). At 1 month, DCE-MRI showed a significant decrease in blood volume (p = 0.0002). IVIM, on the other hand, demonstrated the opposite effect and showed a significant increase in blood volume at 1 month (p = 0.03). The results of this study indicate that blood volume measured with IVIM and DCE-MRI are not equivalent. While this may relate to differences in the type of perfusion information each technique is providing, it could also reflect a limitation of tumor blood volume measurements made with IVIM after SRS. IVIM measurements of tumor blood volume in the month after SRS should therefore be interpreted with caution.

Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney Disease.

Renal disease variability in autosomal dominant polycystic kidney disease (ADPKD) is strongly influenced by the gene locus (PKD1 versus PKD2). Recent studies identified nontruncating PKD1 mutations in approximately 30% of patients who underwent comprehensive mutation screening, but the clinical significance of these mutations is not well defined. We examined the genotype-renal function correlation in a prospective cohort of 220 unrelated ADPKD families ascertained through probands with serum creatinine ≤1.4 mg/dl at recruitment. We screened these families for PKD1 and PKD2 mutations and reviewed the clinical outcomes of the probands and affected family members. Height-adjusted total kidney volume (htTKV) was obtained in 161 affected subjects. Multivariate Cox proportional hazard modeling for renal and patient survival was performed in 707 affected probands and family members. Overall, we identified pathogenic mutations in 84.5% of our families, in which the prevalence of PKD1 truncating, PKD1 in-frame insertion/deletion, PKD1 nontruncating, and PKD2 mutations was 38.3%, 4.3%, 27.1%, and 30.3%, respectively. Compared with patients with PKD1 truncating mutations, patients with PKD1 in-frame insertion/deletion, PKD1 nontruncating, or PKD2 mutations have smaller htTKV and reduced risks (hazard ratio [95% confidence interval]) of ESRD (0.35 [0.14 to 0.91], 0.10 [0.05 to 0.18], and 0.03 [0.01 to 0.05], respectively) and death (0.31 [0.11 to 0.87], 0.20 [0.11 to 0.38], and 0.18 [0.11 to 0.31], respectively). Refined genotype-renal disease correlation coupled with targeted next generation sequencing of PKD1 and PKD2 may provide useful clinical prognostication for ADPKD.