Design and Implementation of an Opt-Out, End-to-End, Preemptive DPYD Testing Program for Patients Planned for a Systemic Fluoropyrimidine.

PURPOSE: Several allelic variants of the gene DPYD encoding dihydropyrimidine dehydrogenase (DPD) are associated with impaired metabolism of the systemic fluoropyrimidine fluorouracil (5FU) and its oral prodrug, capecitabine, which elevates the risk for severe toxicity. Following a patient death related to capecitabine toxicity in which DPD deficiency was suspected, a multidisciplinary advisory panel was convened to develop an institution-wide approach to future patients planned for a systemic fluoropyrimidine. METHODS: The panel selected an opt-out testing strategy which focused on developing reliable processes to collect and report test results and targeted education. An electronic health record-based automated reminder was designed to activate when a 5FU- or capecitabine-containing chemotherapy regimen was ordered for a patient without prior exposure to either agent and without a prior DPYD sequencing test result. DPYD testing was standardized across all sites of care, and a closed loop reporting system for abnormal test results was created. Before implementation, targeted education was provided to providers, pharmacists, and nurses, and a failure mode and effects analysis was performed. Program rollout was staged over a 6-month period. RESULTS: At 10 months, the rate of preemptive testing increased from a baseline of 26% to a sustained rate of >90%. In the six network sites, the testing rate increased from 9% to 96%. A total of 1,043 patients have been tested preemptively; allelic variants have been identified in 43 (4.1%). Among 25 evaluable patients, dose reduction or change to a non-fluoropyrimidine-based regimen was accomplished in 96%. CONCLUSION: Preemptive DPYD testing is feasible, and high rates of testing can be achieved using an opt-out, reminder-based program. We provide the details of the implementation and encourage others to emulate it.

Assessment of arterial pulsatility of cerebral perforating arteries using 7T high-resolution dual-VENC phase-contrast MRI.

PURPOSE: Directly imaging the function of cerebral perforating arteries could provide valuable insight into the pathology of cerebral small vessel diseases (cSVD). Arterial pulsatility has been identified as a useful biomarker for assessing vascular dysfunction. In this study, we investigate the feasibility and reliability of using dual velocity encoding (VENC) phase-contrast MRI (PC-MRI) to measure the pulsatility of cerebral perforating arteries at 7 T. METHODS: Twenty participants, including 12 young volunteers and 8 elder adults, underwent high-resolution 2D PC-MRI scans with VENCs of 20 cm/s and 40 cm/s at 7T. The sensitivity of perforator detection and the reliability of pulsatility measurement of cerebral perforating arteries using dual-VENC PC-MRI were evaluated by comparison with the single-VENC data. The effects of temporal resolution in the PC-MRI acquisition and aging on the pulsatility measurements were investigated. RESULTS: Compared to the single VENCs, dual-VENC PC-MRI provided improved sensitivity of perforator detection and more reliable pulsatility measurements. Temporal resolution impacted the pulsatility measurements, as decreasing temporal resolution led to an underestimation of pulsatility. Elderly adults had elevated pulsatility in cerebral perforating arteries compared to young adults, but there was no difference in the number of detected perforators between the two age groups. CONCLUSION: Dual-VENC PC-MRI is a reliable imaging method for the assessment of pulsatility of cerebral perforating arteries, which could be useful as a potential imaging biomarker of aging and cSVD.

Vessel density mapping of small cerebral vessels on 3D high resolution black blood MRI.

Small cerebral blood vessels are largely inaccessible to existing clinical in vivo imaging technologies. This study aims to present a novel analysis pipeline for vessel density mapping of small cerebral blood vessels from high-resolution 3D black-blood MRI at 3T. Twenty-eight subjects (10 under 35 years old, 18 over 60 years old) were imaged with the T1-weighted turbo spin-echo with variable flip angles (T1w TSE-VFA) sequence optimized for black-blood small vessel imaging with iso-0.5 mm spatial resolution (interpolated from 0.51×0.51×0.64 mm3) at 3T. Hessian-based vessel segmentation methods (Jerman, Frangi and Sato filter) were evaluated by vessel landmarks and manual annotation of lenticulostriate arteries (LSAs). Using optimized vessel segmentation, large vessel pruning and non-linear registration, a semiautomatic pipeline was proposed for quantification of small vessel density across brain regions and further for localized detection of small vessel changes across populations. Voxel-level statistics was performed to compare vessel density between two age groups. Additionally, local vessel density of aged subjects was correlated with their corresponding gross cognitive and executive function (EF) scores using Montreal Cognitive Assessment (MoCA) and EF composite scores compiled with Item Response Theory (IRT). Jerman filter showed better performance for vessel segmentation than Frangi and Sato filter which was employed in our pipeline. Small cerebral blood vessels including small artery, arterioles, small veins, and venules on the order of a few hundred microns can be delineated using the proposed analysis pipeline on 3D black-blood MRI at 3T. The mean vessel density across brain regions was significantly higher in young subjects compared to aged subjects. In the aged subjects, localized vessel density was positively correlated with MoCA and IRT EF scores. The proposed pipeline is able to segment, quantify, and detect localized differences in vessel density of small cerebral blood vessels based on 3D high-resolution black-blood MRI. This framework may serve as a tool for localized detection of small vessel density changes in normal aging and cerebral small vessel disease.

Next-generation MRI scanner designed for ultra-high-resolution human brain imaging at 7 Tesla.

To increase granularity in human neuroimaging science, we designed and built a next-generation 7 Tesla magnetic resonance imaging scanner to reach ultra-high resolution by implementing several advances in hardware. To improve spatial encoding and increase the image signal-to-noise ratio, we developed a head-only asymmetric gradient coil (200 mT m-1, 900 T m-1s-1) with an additional third layer of windings. We integrated a 128-channel receiver system with 64- and 96-channel receiver coil arrays to boost signal in the cerebral cortex while reducing g-factor noise to enable higher accelerations. A 16-channel transmit system reduced power deposition and improved image uniformity. The scanner routinely performs functional imaging studies at 0.35-0.45 mm isotropic spatial resolution to reveal cortical layer functional activity, achieves high angular resolution in diffusion imaging and reduces acquisition time for both functional and structural imaging.

Deep learning-based local SAR prediction using B1 maps and structural MRI of the head for parallel transmission at 7 T.

PURPOSE: To predict subject-specific local specific absorption rate (SAR) distributions of the human head for parallel transmission (pTx) systems at 7 T. THEORY AND METHODS: Electromagnetic energy deposition in tissues is nonuniform at 7 T, and interference patterns due to individual channels of pTx systems may result in increased local SAR values, which can only be estimated with very high safety margins. We proposed, designed, and demonstrated a multichannel 3D convolutional neural network (CNN) architecture to predict local SAR maps as well as peak-spatial SAR (ps-SAR) levels. We hypothesized that utilizing a three-channel 3D CNN, in which each channel is fed by a B 1 + $$ {B}_1^{+} $$ map, a phase-reversed B 1 + $$ {B}_1^{+} $$ map, and an MR image, would improve prediction accuracies and decrease uncertainties in the predictions. We generated 10 new head-neck body models, along with 389 3D pTx MRI data having different RF shim settings, with their B1 and local SAR maps to support efforts in this field. RESULTS: The proposed three-channel 3D CNN predicted ps-SAR10g levels with an average overestimation error of 20%, which was better than the virtual observation points-based estimation error (i.e., 152% average overestimation). The proposed method decreased prediction uncertainties over 20% (i.e., 22.5%-17.7%) compared to other methods. A safety factor of 1.20 would be enough to avoid underestimations for the dataset generated in this work. CONCLUSION: Multichannel 3D CNN networks can be promising in predicting local SAR values and perform predictions within a second, making them clinically useful as an alternative to virtual observation points-based methods.

Whole-Cerebrum distortion-free three-dimensional pseudo-continuous arterial spin labeling at 7T.

Fulfilling potentials of ultrahigh field for pseudo-Continuous Arterial Spin Labeling (pCASL) has been hampered by B1/B0 inhomogeneities that affect pCASL labeling, background suppression (BS), and the readout sequence. This study aimed to present a whole-cerebrum distortion-free three-dimensional (3D) pCASL sequence at 7T by optimizing pCASL labeling parameters, BS pulses, and an accelerated Turbo-FLASH (TFL) readout. A new set of pCASL labeling parameters (Gave = 0.4 mT/m, Gratio = 14.67) was proposed to avoid interferences in bottom slices while achieving robust labeling efficiency (LE). An OPTIM BS pulse was designed based on the range of B1/B0 inhomogeneities at 7T. A 3D TFL readout with 2D-CAIPIRINHA undersampling (R = 2 × 2) and centric ordering was developed, and the number of segments (Nseg) and flip angle (FA) were varied in simulation to achieve the optimal trade-off between SNR and spatial blurring. In-vivo experiments were performed on 19 subjects. The results showed that the new set of labeling parameters effectively achieved whole-cerebrum coverage by eliminating interferences in bottom slices while maintaining a high LE. The OPTIM BS pulse achieved 33.3% higher perfusion signal in gray matter (GM) than the original BS pulse with a cost of 4.8-fold SAR. Incorporating a moderate FA (8°) and Nseg (2), whole-cerebrum 3D TFL-pCASL imaging was achieved with a 2 × 2 × 4 mm3 resolution without distortion and susceptibility artifacts compared to 3D GRASE-pCASL. In addition, 3D TFL-pCASL showed a good to excellent test-retest repeatability and potential of higher resolution (2 mm isotropic). The proposed technique also significantly improved SNR when compared to the same sequence at 3T and simultaneous multislice TFL-pCASL at 7T. By combining a new set of labeling parameters, OPTIM BS pulse, and accelerated 3D TFL readout, we achieved high resolution pCASL at 7T with whole-cerebrum coverage, detailed perfusion and anatomical information without distortion, and sufficient SNR.

Whole-Cerebrum distortion-free three-dimensional pseudo-Continuous Arterial Spin Labeling at 7T.

Fulfilling potentials of ultrahigh field for pseudo-Continuous Arterial Spin Labeling (pCASL) has been hampered by B1/B0 inhomogeneities that affect pCASL labeling, background suppression (BS), and the readout sequence. This study aimed to present a whole-cerebrum distortion-free three-dimensional (3D) pCASL sequence at 7T by optimizing pCASL labeling parameters, BS pulses, and an accelerated Turbo-FLASH (TFL) readout. A new set of pCASL labeling parameters (Gave=0.4mT/m, Gratio=14.67) was proposed to avoid interferences in bottom slices while achieving robust labeling efficiency (LE). An OPTIM BS pulse was designed based on the range of B1/B0 inhomogeneities at 7T. A 3D TFL readout with 2D-CAIPIRINHA undersampling (R=2×2) and centric ordering was developed, and the number of segments (Nseg) and flip angle (FA) were varied in simulation to achieve the optimal trade-off between SNR and spatial blurring. In-vivo experiments were performed on 19 subjects. The results showed that the new set of labeling parameters effectively achieved whole-cerebrum coverage by eliminating interferences in bottom slices while maintaining a high LE. The OPTIM BS pulse achieved 33.3% higher perfusion signal in gray matter (GM) than the original BS pulse with a cost of 4.8-fold SAR. Incorporating a moderate FA (8 ° ) and Nseg (2), whole-cerebrum 3D TFL-pCASL imaging was achieved with a 2×2×4 mm 3 resolution without distortion and susceptibility artifacts compared to 3D GRASE-pCASL. In addition, 3D TFL-pCASL showed a good to excellent test-retest repeatability and potential of higher resolution (2 mm isotropic). The proposed technique also significantly improved SNR when compared to the same sequence at 3T and simultaneous multislice TFL-pCASL at 7T. By combining a new set of labeling parameters, OPTIM BS pulse, and accelerated 3D TFL readout, we achieved high resolution pCASL at 7T with whole-cerebrum coverage, detailed perfusion and anatomical information without distortion, and sufficient SNR.

Vessel Density Mapping of Cerebral Small Vessels on 3D High Resolution Black Blood MRI.

Cerebral small vessels are largely inaccessible to existing clinical in vivo imaging technologies. This study aims to present a novel analysis pipeline for vessel density mapping of cerebral small vessels from high-resolution 3D black-blood MRI at 3T. Twenty-eight subjects (10 under 35 years old, 18 over 60 years old) were imaged with the T1-weighted turbo spin-echo with variable flip angles (T1w TSE-VFA) sequence optimized for black-blood small vessel imaging with iso-0.5mm spatial resolution at 3T. Hessian-based vessel segmentation methods (Jerman, Frangi and Sato filter) were evaluated by vessel landmarks and manual annotation of lenticulostriate arteries (LSAs). Using optimized vessel segmentation, large vessel pruning and non-linear registration, a semiautomatic pipeline was proposed for quantification of small vessel density across brain regions and further for localized detection of small vessel changes across populations. Voxel-level statistics was performed to compare vessel density between two age groups. Additionally, local vessel density of aged subjects was correlated with their corresponding gross cognitive and executive function (EF) scores using Montreal Cognitive Assessment (MoCA) and EF composite scores compiled with Item Response Theory (IRT). Jerman filter showed better performance for vessel segmentation than Frangi and Sato filter which was employed in our pipeline. Cerebral small vessels on the order of a few hundred microns can be delineated using the proposed analysis pipeline on 3D black-blood MRI at 3T. The mean vessel density across brain regions was significantly higher in young subjects compared to aged subjects. In the aged subjects, localized vessel density was positively correlated with MoCA and IRT EF scores. The proposed pipeline is able to segment, quantify, and detect localized differences in vessel density of cerebral small vessels based on 3D high-resolution black-blood MRI. This framework may serve as a tool for localized detection of small vessel density changes in normal aging and cerebral small vessel disease.

The Experience of 3D Total-Body Photography to Monitor Nevi: Results From an Australian General Population-Based Cohort Study.

BACKGROUND: Digital 3D total-body photography of the skin surface is an emerging imaging modality that can facilitate the identification of new and changing nevi. OBJECTIVE: We aimed to describe the experiences of study participants drawn from the general population who were provided 3D total-body photography and dermoscopy for the monitoring of nevi. METHODS: A population-based prospective study of adults aged 20-70 years from South East Queensland, Australia was conducted. Participants underwent 3D total-body photography and dermoscopy every 6 months over a 3-year period. Participants were asked to provide closed and open-ended feedback on their 3D total-body photography and dermoscopy experience (eg, comfort, trust, intended future use, and willingness to pay) at the halfway study time point (18 months) and final study time point (36 months). We assessed changes in participants' reported experience of 3D total-body photography, and patient characteristics associated with patient experience at the end of the study (36 months) were analyzed. RESULTS: A total of 149 participants completed the surveys at both the 18- and 36-month time points (median age 55, range 23-70 years; n=94, 63.1% were male). At the 18-month time point, most participants (n=103, 69.1%) stated they completely trusted 3D total-body imaging for the diagnosis and monitoring of their nevi, and this did not change at the 36-month (n=104, 69.8%) time point. The majority of participants reported that they were very comfortable or comfortable with the technology at both the 18- (n=138, 92.6%) and 36-month (n=140, 94%) time points, respectively; albeit, the number of participants reporting that they were very comfortable reduced significantly between the 18- and 36-month time points, from 71.1% (n=106) to 61.1% (n=91; P=.01). Almost all participants (n=140, 94%) would consider using this technology if it were to become commercially available, and this did not change during the two study time points. Half of the participants (n=74) cited barriers to participating in 3D total-body photography, including trust in the ability of this technology to detect and monitor suspicious lesions, digital privacy, cost, and travel requirements. CONCLUSIONS: The majority of participants expressed positive attitudes toward 3D total-body photography for the monitoring of their moles. Half of the participants identified potential barriers to uptake.

Optimization of pseudo-continuous arterial spin labeling at 7T with parallel transmission B1 shimming.

PURPOSE: To optimize pseudo-continuous arterial spin labeling (pCASL) for 7 T, and to further improve the labeling efficiency with parallel RF transmission transmit B1 ( B1+ ) shimming. METHODS: pCASL parameters were optimized based on B1+/B0 field distributions at 7 T with simulation. To increase labeling efficiency, the B1+ amplitude at inflowing arteries was increased with parallel RF transmission B1+ shimming. The "indv-shim" with shimming weights calculated for each individual subject, and the "univ-shim" with universal weights calculated on a group of 12 subjects, were compared with circular polarized (CP) shim. The optimized pCASL sequences with three B1+ shimming modes (indv-shim, univ-shim, and CP-shim) were evaluated in 6 subjects who underwent two repeated scans 24 hours apart, along with a pulsed ASL sequence. Quantitative metrics including mean B1+ amplitude, perfusion, and intraclass correlation coefficient were calculated. The optimized 7T pCASL was compared with standard 3T pCASL on 5 subjects, using spatial SNR and temporal SNR. RESULTS: The optimal pCASL parameter set (RF duration/gap = 300/250 us, Gave=0.6mT/m,gRatio=10 ) achieved robust perfusion measurement in the presence of B1+/B0 inhomogeneities. Both indv-shim and univ-shim significantly increased B1+ amplitude compared with CP-shim in simulation and in vivo experiment (P < .01). Compared with CP-shim, perfusion signal was increased by 9.5% with indv-shim (P < .05) and by 5.3% with univ-shim (P = .35). All three pCASL sequences achieved fair to good repeatability (intraclass correlation coefficient ≥ 0.5). Compared with 3T pCASL, the optimized 7T pCASL achieved 78.3% higher spatial SNR and 200% higher temporal SNR. CONCLUSION: The optimized pCASL achieved robust perfusion imaging at 7 T, while both indv-shim and univ-shim further increased labeling efficiency.

Evaluation of Cerebral Blood Flow Measured by 3D PCASL as Biomarker of Vascular Cognitive Impairment and Dementia (VCID) in a Cohort of Elderly Latinx Subjects at Risk of Small Vessel Disease.

Cerebral small vessel disease (cSVD) affects arterioles, capillaries, and venules and can lead to cognitive impairments and clinical symptomatology of vascular cognitive impairment and dementia (VCID). VCID symptoms are similar to Alzheimer's disease (AD) but the neurophysiologic alterations are less well studied, resulting in no established biomarkers. The purpose of this study was to evaluate cerebral blood flow (CBF) measured by 3D pseudo-continuous arterial spin labeling (pCASL) as a potential biomarker of VCID in a cohort of elderly Latinx subjects at risk of cSVD. Forty-five elderly Latinx subjects (12 males, 69 ± 7 years) underwent repeated MRI scans ∼6 weeks apart. CBF was measured using 3D pCASL in the whole brain, white matter and 4 main vascular territories (leptomeningeal anterior, middle, and posterior cerebral artery (leptoACA, leptoMCA, leptoPCA), as well as MCA perforator). The test-retest repeatability of CBF was assessed by intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wsCV). Absolute and relative CBF was correlated with gross cognitive measures and domain specific assessment of executive and memory function, vascular risks, and Fazekas scores and volumes of white matter hyperintensity (WMH). Neurocognitive evaluations were performed using Montreal Cognitive Assessment (MoCA) and neuropsychological test battery in the Uniform Data Set v3 (UDS3). Good to excellent test-retest repeatability was achieved (ICC = 0.77-0.85, wsCV 3-9%) for CBF measurements in the whole brain, white matter, and 4 vascular territories. Relative CBF normalized by global mean CBF in the leptoMCA territory was positively correlated with the executive function composite score, while relative CBF in the leptoMCA and MCA perforator territory was positively correlated with MoCA scores, controlling for age, gender, years of education, and testing language. Relative CBF in WM was negatively correlated with WMH volume and MoCA scores, while relative leptoMCA CBF was positively correlated with WMH volume. Reliable 3D pCASL CBF measurements were achieved in the cohort of elderly Latinx subjects. Relative CBF in the leptomeningeal and perforator MCA territories were the most likely candidate biomarker of VCID. These findings need to be replicated in larger cohorts with greater variability of stages of cSVD.

Optimization of adiabatic pulses for pulsed arterial spin labeling at 7 tesla: Comparison with pseudo-continuous arterial spin labeling.

PURPOSE: To optimize and evaluate adiabatic pulses for pulsed arterial spin labeling at ultrahigh field 7 tesla. METHODS: Four common adiabatic inversion pulses, including hyperbolic secant, wideband uniform rate smooth truncation, frequency offset corrected inversion, and time-resampled frequency offset corrected inversion pulses, were optimized based on a custom-defined loss function that included labeling efficiency and inversion band uniformity. The optimized pulses were implemented in flow-sensitive alternating inversion recovery sequences and tested on phantom and 11 healthy volunteers with 2 constraints: 1) specific absorption rate normalized; and 2) equal peak RF amplitude, respectively. A pseudo-continuous arterial spin labeling sequence was implemented for comparison. Quantitative metrics such as perfusion and relative labeling efficiency versus residual tissue signal were calculated. RESULTS: Among the 4 pulses, the wideband uniform rate smooth truncation pulse yielded the lowest loss in simulation and achieved a good balance between labeling efficiency and residual tissue signal from both phantom and in vivo experiments. Wideband uniform rate smooth truncation-pulsed arterial spin labeling showed significantly higher relative labeling efficiency compared to the other sequences (P < .01), whereas the perfusion signal was increased by 40% when the highest B1+ amplitude was used. The 4 pulsed arterial spin labeling sequences yielded comparable perfusion signals compared to pseudo-continuous arterial spin labeling but with less than half the specific absorption rate. CONCLUSION: Optimized wideband uniform rate smooth truncation pulse with the highest B1+ amplitude allowed was recommended for 7 tesla pulsed arterial spin labeling.

Brain arteriolosclerosis.

Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here, we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as Alzheimer's disease and limbic-predominant age-related TDP-43 encephalopathy (LATE). There may also be complex physiologic interactions between metabolic syndrome (e.g., hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that factored in comorbid diseases, B-ASC was independently associated with impairments of global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80 years of age, B-ASC is a complex and under-studied contributor to neurologic disability.

Cerebroarterial pulsatility and resistivity indices are associated with cognitive impairment and white matter hyperintensity in elderly subjects: A phase-contrast MRI study.

Increased cerebroarterial pulsations are thought to be contributing factors in microvascular damage and cognitive impairment. In this study, we assessed the utility of two-dimensional (2D) phase-contrast MRI (PC-MRI) in quantifying cerebroarterial pulsations and evaluated the associations of pulsatile and non-pulsatile hemodynamic measures with cognitive performance and white matter hyperintensities (WMH). Neurocognitive assessments on 50 elderly subjects were performed using clinical dementia rating (CDR) and Montreal cognitive assessment (MoCA). An electrocardiogram-gated 2D PC-MRI sequence was used to calculate mean flow rate, pulsatility index (PI), and resistivity index (RI) of the internal carotid artery. For each subject, whole brain global cerebral blood flow (gCBF) and relative WMH volume were also quantified. Elevated RI was significantly associated with reduced cognitive performance quantified using MoCA (p = 0.04) and global CDR (p = 0.02). PI and RI were both significantly associated with relative WMH volume (p = 0.01, p < 0.01, respectively). However, non-pulsatile hemodynamic measures were not associated with cognitive impairment or relative WMH volume. This study showed that the cerebroarterial pulsatile measures obtained using PC-MRI have stronger association with the measures of cognitive impairment compared to global blood flow measurement and as such, might be useful as potential biomarkers of cerebrovascular dysfunction in preclinical populations.

Semiautomatic cerebrovascular territory mapping based on dynamic ASL MR angiography without vessel-encoded labeling.

PURPOSE: Characterizing vessel territories can provide crucial information for evaluation of cerebrovascular disorders. In this study, we present a novel postprocessing pipeline for vascular territorial imaging of cerebral arteries based on a noncontrast enhanced time-resolved 4D magnetic resonance angiography (MRA). METHODS: Eight healthy participants, 1 Moyamoya patient, and 1 arteriovenous malformations patient were recruited. Territorial segmentation and relative blood flow rate calculations of cerebral arteries including left and right middle cerebral arteries and left and right posterior cerebral arteries were carried out based on the 4D MRA-derived arterial arrival time maps of intracranial vessels. RESULTS: Among healthy young subjects, the average relative blood flow rate values corresponding to left and right middle cerebral arteries and left and right posterior cerebral arteries were 35.9 ± 5.9%, 32.9 ± 7.5%, 15.4 ± 3.8%, and 15.9 ± 2.5%, respectively. Excellent agreement was observed between relative blood flow rate values obtained from the proposed 4D MRA-based method and reference 2D phase contrast MRI. Abnormal cerebral circulations were visualized and quantified on both patients using the developed technique. CONCLUSION: The vascular territorial imaging technique developed in this study allowed for the generation of territorial maps with user-defined level of details within a clinically feasible scan time, and as such may provide useful information to assess cerebral circulation balance in different pathologies.

High-Resolution Neurovascular Imaging at 7T: Arterial Spin Labeling Perfusion, 4-Dimensional MR Angiography, and Black Blood MR Imaging.

Ultrahigh field offers increased resolution and contrast for neurovascular imaging. Arterial spin labeling methods benefit from an increased intrinsic signal-to-noise ratio of MR imaging signal and a prolonged tracer half-life at ultrahigh field, allowing the visualization of layer-dependent microvascular perfusion. Arterial spin labeling-based time-resolved 4-dimensional MR angiography at 7T provides a detailed depiction of the vascular architecture and dynamic blood flow pattern with high spatial and temporal resolutions. High-resolution black blood MR imaging at 7T allows detailed characterization of small perforating arteries such as lenticulostriate arteries. All techniques benefit from advances in parallel radiofrequency transmission technologies at ultrahigh field.

Comparison Between Blood-Brain Barrier Water Exchange Rate and Permeability to Gadolinium-Based Contrast Agent in an Elderly Cohort.

Background: Dynamic contrast-enhanced (DCE) MRI using intravenous injection of gadolinium-based contrast agents (GBCAs) is commonly used for imaging blood-brain barrier (BBB) permeability. Water is an alternative endogenous tracer with limited exchange rate across the BBB. A direct comparison between BBB water exchange rate and BBB permeability to GBCA is missing. The purpose of this study was to directly compare BBB permeability to GBCA (Ktrans and kGad = Ktrans/Vp) and water exchange rate (kw) in a cohort of elderly subjects at risk of cerebral small vessel disease (cSVD). Methods: Ktrans/kGad and kw were measured by DCE-MRI and diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL), respectively, at 3 Tesla in 16 elderly subjects (3 male, age = 67.9 ± 3.0 yrs) at risk of cSVD. The test-retest reproducibility of kw measurements was evaluated with repeated scans ~6 weeks apart. Mixed effects linear regression was performed in the whole brain, gray matter (GM), white matter (WM), and 6 subcortical brain regions to investigate associations between Ktrans/kGad and test-retest kw. In addition, kw and Ktrans/kGad were compared in normal appearing white matter (NAWM), white matter hyperintensity (WMH) lesions and penumbra. Results: Significant correlation was found between kw and Ktrans only in WM (ß = 6.7 × 104, P = 0.036), caudate (ß = 8.6 × 104, P = 0.029), and middle cerebral artery (MCA) perforator territory (ß = 6.9 × 104, P = 0.009), but not in the whole brain, GM or rest 5 brain regions. Significant correlation was found between kw and kGad in MCA perforator territory (ß = 1.5 × 103, P = 0.049), medial-temporal lobe (ß = 3.5 × 103, P = 0.032), and hippocampus (ß = 3.4 × 103, P = 0.038), but not in the rest brain regions. Good reproducibility of kw measurements (ICC=0.75) was achieved. Ktrans was significantly lower inside WMH than WMH penumbra (16.2%, P = 0.026), and kGad was significantly lower in NAWM than in the WMH penumbra (20.8%, P < 0.001). Conclusion: kw provides a measure of water exchange rate across the BBB with good test-retest reproducibility. The BBB mechanism underlying kw and Ktrans/kGad is likely to be different, as manifested by correlations in only three brain regions for each pair of comparison between kw and Ktrans or kGad.

Lower retinal capillary density in minimal cognitive impairment among older Latinx adults.

INTRODUCTION: We investigated the hypothesis that retinal capillary perfusion is a biomarker of early cognitive decline and cerebrovascular perfusion associated with small vessel disease in a pilot data set of Latinx adults at high risk for vascular cognitive impairment and dementia. METHODS: High-resolution optical coherence tomography angiography (OCTA) images were acquired from dilated eyes of Latinx subjects using a 3 × 3 mm2 scan pattern from a commercially available device. A previously validated method was used to quantify the density of perfused retinal capillaries as the retinal vessel skeleton density (VSD). The association of VSD with Clinical Dementia Rating Sum of Boxes, total Montreal Cognitive Assessment (MoCA) score, and individual MoCA test elements were analyzed using multivariate statistics that adjusted for confounders. VSD was also compared with magnetic resonance imaging (MRI) measures of cerebrovascular reactivity (CVR) and perfusion in the middle cerebral artery perforator (MCA-Perf) territory. RESULTS: The mean (± SD) age of the subjects was 68 (± 6) years. For every 0.01-unit lower VSD, the risk of having a CDR-SOB >0 was 20% higher (95%CI = 5%-90%; P = .031). Similarly, a lower VSD was associated with lower total MoCA score (r = 0.3; P = .038). The Visuospatial/Executive domain of the MoCA assessment showed the strongest association with VSD ( ß  = 0.02; P = .022). Lower retinal VSD was associated with worse MRI measure of CVR (r = 0.7, P = .04) and less perfusion in the MCA-Perf territory (r = 0.45, P = .02). DISCUSSION: Impaired retinal capillary perfusion is associated with cognitive impairment and abnormalities in cerebrovascular perfusion and function. OCTA-based retinal capillary assessment holds promise for identifying and quantifying retinal correlates of neurovascular abnormalities associated with vascular cognitive impairment.

Reperfusion Into Severely Damaged Brain Tissue Is Associated With Occurrence of Parenchymal Hemorrhage for Acute Ischemic Stroke.

Background and Purpose: This study aims to quantify the reperfusion status within severely damaged brain tissue and to evaluate its relationship with high grade of hemorrhagic transformation (HT). Methods: Pseudo-continuous ASL was performed along with DWI in 102 patients within 24 h post-treatments. The infarction core was identified using ADC values <550 × 10-6 mm2/s. CBF within the infarction core and its contralateral counterpart were acquired. CBF at the 25th, median, and 75th percentiles of the contralateral counterpart were used as thresholds and the ASL reperfusion volume above the threshold was labeled as vol-25, -50, and -75, respectively. Recanalization was defined according to Thrombolysis in Myocardial Infarction (TIMI) criteria. Results: Quantified reperfusion within the infarction core differed significantly in patients with complete and incomplete recanalization. In the ROC analysis for the prediction of parenchymal hematoma (PH), ASL reperfusion vol-25 had the highest area under the curve (AUC) when compared with ASL vol-50 and ASL vol-75. ASL reperfusion vol-25 had significantly higher AUC compared with ADC threshold volume in the prediction of PH (0.783 vs. 0.685, P = 0.0036) and PH-2 (0.844 vs. 0.754, P = 0.0035). In stepwise multivariate logistic regression analysis, only ASL reperfusion vol-25 emerged as an independent predictor of PH (OR = 3.51, 95% CI: 1.65-7.45, P < 0.001) and PH-2 (OR = 2.32, 95% CI: 1.13-4.76, P = 0.022). Conclusions: Increased reperfusion volume within severely damaged brain tissue is associated with the occurrence of higher grade of HT.

The Jacki Jacket after mastectomy with reconstruction: a randomized pilot study.

BACKGROUND: Breast cancer patients undergoing mastectomy with reconstruction (TM + R) often experience post-operative discomfort from surgical drains. Despite a variety of garment options for use in the post-operative period, high-quality data assessing the impact of specific garments on post-operative pain are lacking. We report the results of a prospective randomized trial assessing the impact of the Jacki Jacket (JJ), a long-sleeve jacket with inner drain receptacle pockets, on post-discharge pain and quality of life (QOL) after TM + R. METHODS: Breast cancer patients undergoing TM + R at a single institution were randomized post-operatively to receive a JJ or usual care (UC). Participant-reported demographics, pain intensity, and QOL were collected on post-operative day 1 (T1). Following discharge, participants completed a daily pain and medication dairy (T2); on day of drain(s) removal (T3), participants again completed pain and QOL questionnaires. Linear models were used to evaluate associations between JJ use, post-operative pain, and QOL. RESULTS: From 3/8/17 to 12/20/17, 139 women were randomized. All participants completed T1 measures, 102 returned the T2 diary, and 118 (84.9%) completed T3 questionnaires. There was no significant difference in pain scores between JJ and UC arms at any timepoint. Adjusting for surgery type, age, marital status, depression, and obesity, participants randomized to JJ reported significantly better body image scores (estimate = 12.94, p = 0.009). There were no adverse events. CONCLUSIONS: Although JJ garment use did not impact post-operative pain intensity scores, the significant impact of JJ use on body image supports consideration for inclusion of such garments in post-operative care for patients undergoing TM + R. CLINICAL TRIAL REGISTRATION INFORMATION: Registered with ClinicalTrials.gov, NCT number NCT02976103, November 18, 2016.