Gender Disparity in Industry Relationships With Academic Interventional Radiology Physicians.

OBJECTIVE. Industry relationships drive technologic innovation in interventional radiology and offer opportunities for professional growth. Women are underrepresented in interventional radiology despite the growing recognition of the importance of diversity. This study characterized gender disparities in financial relationships between industry and academic interventional radiologists. MATERIALS AND METHODS. In this retrospective cross-sectional study, U.S. academic interventional radiology physicians and their academic ranks were identified by searching websites of practices with accredited interventional radiology fellowship programs. Publicly available databases were queried to collect each physician's gender, years since medical school graduation, h-index, academic rank, and industry payments in 2018. Wilcoxon and chi-square tests compared payments between genders. A general linear model assessed the impact of academic rank, years since graduation, gender, and h-index on payments. RESULTS. Of 842 academic interventional radiology physicians, 108 (13%) were women. A total $14,206,599.41 was received by 686 doctors (81%); only $147,975.28 (1%) was received by women. A lower percentage of women (74%) than men (83%) received payments (p = 0.04); median total payments were lower for women ($535) than men ($792) (p = 0.01). Academic rank, h-index, years since graduation, and male gender were independent predictors of higher payments. Industry payments supporting technologic advancement were made exclusively to men. CONCLUSION. Female interventional radiology physicians received fewer and lower industry payments, earning 1% of total payments despite constituting 13% of physicians. Gender independently predicted industry payments, regardless of h-index, academic rank, or years since graduation. Gender disparity in interventional radiology physician-industry relationships warrants further investigation and correction.

Intravenous thrombolysis in unwitnessed stroke onset: MR WITNESS trial results.

OBJECTIVE: Most acute ischemic stroke (AIS) patients with unwitnessed symptom onset are ineligible for intravenous thrombolysis due to timing alone. Lesion evolution on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) correlates with stroke duration, and quantitative mismatch of diffusion-weighted MRI with FLAIR (qDFM) might indicate stroke duration within guideline-recommended thrombolysis. We tested whether intravenous thrombolysis ≤4.5 hours from the time of symptom discovery is safe in patients with qDFM in an open-label, phase 2a, prospective study (NCT01282242). METHODS: Patients aged 18 to 85 years with AIS of unwitnessed onset at 4.5 to 24 hours since they were last known to be well, treatable within 4.5 hours of symptom discovery with intravenous alteplase (0.9mg/kg), and presenting with qDFM were screened across 14 hospitals. The primary outcome was the risk of symptomatic intracranial hemorrhage (sICH) with preplanned stopping rules. Secondary outcomes included symptomatic brain edema risk, and functional outcomes of 90-day modified Rankin Scale (mRS). RESULTS: Eighty subjects were enrolled between January 31, 2011 and October 4, 2015 and treated with alteplase at median 11.2 hours (IQR = 9.5-13.3) from when they were last known to be well. There was 1 sICH (1.3%) and 3 cases of symptomatic edema (3.8%). At 90 days, 39% of subjects achieved mRS = 0-1, as did 48% of subjects who had vessel imaging and were without large vessel occlusions. INTERPRETATION: Intravenous thrombolysis within 4.5 hours of symptom discovery in patients with unwitnessed stroke selected by qDFM, who are beyond the recommended time windows, is safe. A randomized trial testing efficacy using qDFM appears feasible and is warranted in patients without large vessel occlusions. Ann Neurol 2018;83:980-993.

Diffusion tensor imaging in acute-to-subacute traumatic brain injury: a longitudinal analysis.

BACKGROUND: Diffusion tensor imaging (DTI) may have prognostic utility in patients with traumatic brain injury (TBI), but the optimal timing of DTI data acquisition is unknown because of dynamic changes in white matter water diffusion during the acute and subacute stages of TBI. We aimed to characterize the direction and magnitude of early longitudinal changes in white matter fractional anisotropy (FA) and to determine whether acute or subacute FA values correlate more reliably with functional outcomes after TBI. METHODS: From a prospective TBI outcomes database, 11 patients who underwent acute (≤7 days) and subacute (8 days to rehabilitation discharge) DTI were retrospectively analyzed. Longitudinal changes in FA were measured in 11 white matter regions susceptible to traumatic axonal injury. Correlations were assessed between acute FA, subacute FA and the disability rating scale (DRS) score, which was ascertained at discharge from inpatient rehabilitation. RESULTS: FA declined from the acute-to-subacute period in the genu of the corpus callosum (0.70 ± 0.02 vs. 0.55 ± 0.11, p < 0.05) and inferior longitudinal fasciculus (0.54+/-0.07 vs. 0.49+/-0.07, p < 0.01). Acute correlations between FA and DRS score were variable: higher FA in the body (R = -0.78, p = 0.02) and splenium (R = -0.83, p = 0.003) of the corpus callosum was associated with better outcomes (i.e. lower DRS scores), whereas higher FA in the genu of the corpus callosum (R = 0.83, p = 0.02) corresponded with worse outcomes (i.e. higher DRS scores). In contrast, in the subacute period higher FA in the splenium correlated with better outcomes (R = -0.63, p < 0.05) and no inverse correlations were observed. CONCLUSIONS: White matter FA declined during the acute-to-subacute stages of TBI. Variability in acute FA correlations with outcome suggests that the optimal timing of DTI for TBI prognostication may be in the subacute period.

Longitudinal Diffusion Tensor Imaging Detects Recovery of Fractional Anisotropy Within Traumatic Axonal Injury Lesions.

BACKGROUND: Traumatic axonal injury (TAI) may be reversible, yet there are currently no clinical imaging tools to detect axonal recovery in patients with traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to characterize serial changes in fractional anisotropy (FA) within TAI lesions of the corpus callosum (CC). We hypothesized that recovery of FA within a TAI lesion correlates with better functional outcome. METHODS: Patients who underwent both an acute DTI scan (≤day 7) and a subacute DTI scan (day 14 to inpatient rehabilitation discharge) at a single institution were retrospectively analyzed. TAI lesions were manually traced on the acute diffusion-weighted images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were measured within the TAI lesions at each time point. FA recovery was defined by a longitudinal increase in CC FA that exceeded the coefficient of variation for FA based on values from healthy controls. Acute FA, ADC, AD, and RD were compared in lesions with and without FA recovery, and correlations were tested between lesional FA recovery and functional recovery, as determined by disability rating scale score at discharge from inpatient rehabilitation. RESULTS: Eleven TAI lesions were identified in 7 patients. DTI detected FA recovery within 2 of 11 TAI lesions. Acute FA, ADC, AD, and RD did not differ between lesions with and without FA recovery. Lesional FA recovery did not correlate with disability rating scale scores. CONCLUSIONS: In this retrospective longitudinal study, we provide initial evidence that FA can recover within TAI lesions. However, FA recovery did not correlate with improved functional outcomes. Prospective histopathological and clinical studies are needed to further elucidate whether lesional FA recovery indicates axonal healing and has prognostic significance.

Role of Acute Lesion Topography in Initial Ischemic Stroke Severity and Long-Term Functional Outcomes.

BACKGROUND AND PURPOSE: Acute infarct volume, often proposed as a biomarker for evaluating novel interventions for acute ischemic stroke, correlates only moderately with traditional clinical end points, such as the modified Rankin Scale. We hypothesized that the topography of acute stroke lesions on diffusion-weighted magnetic resonance imaging may provide further information with regard to presenting stroke severity and long-term functional outcomes. METHODS: Data from a prospective stroke repository were limited to acute ischemic stroke subjects with magnetic resonance imaging completed within 48 hours from last known well, admission NIH Stroke Scale (NIHSS), and 3-to-6 months modified Rankin Scale scores. Using voxel-based lesion symptom mapping techniques, including age, sex, and diffusion-weighted magnetic resonance imaging lesion volume as covariates, statistical maps were calculated to determine the significance of lesion location for clinical outcome and admission stroke severity. RESULTS: Four hundred ninety subjects were analyzed. Acute stroke lesions in the left hemisphere were associated with more severe NIHSS at admission and poor modified Rankin Scale at 3 to 6 months. Specifically, injury to white matter (corona radiata, internal and external capsules, superior longitudinal fasciculus, and uncinate fasciculus), postcentral gyrus, putamen, and operculum were implicated in poor modified Rankin Scale. More severe NIHSS involved these regions, as well as the amygdala, caudate, pallidum, inferior frontal gyrus, insula, and precentral gyrus. CONCLUSIONS: Acute lesion topography provides important insights into anatomic correlates of admission stroke severity and poststroke outcomes. Future models that account for infarct location in addition to diffusion-weighted magnetic resonance imaging volume may improve stroke outcome prediction and identify patients likely to benefit from aggressive acute intervention and personalized rehabilitation strategies.

Improving door-to-needle times: a single center validation of the target stroke hypothesis.

BACKGROUND AND PURPOSE: National guidelines recommend imaging within 25 minutes of emergency department arrival and intravenous tissue-type plasminogen activator within 60 minutes of emergency department arrival for patients with acute stroke. In 2007, we implemented a new institutional acute stroke care model to include 10 best practices and evaluated the effect of this intervention on improving door-to-computed tomography (CT) and door-to-needle (DTN) times at our hospital. METHODS: We compared patients who presented directly to our hospital with acute ischemic stroke in the preintervention (2003-2006) and postintervention (2008-2011) periods. We did not include 2007, the year that the new protocol was established. Predictors of DTN ≤60 minutes before and after the intervention were assessed using χ(2) for categorical variables, and t test and Wilcoxon signed-rank test for continuous variables. RESULTS: Among 2595 patients with acute stroke, 284 (11%) received intravenous tissue-type plasminogen activator. For patients arriving within an intravenous tissue-type plasminogen activator window, door-to-CT <25 improved from 26.7% pre intervention to 52.3% post intervention (P<0.001). Similarly, the percentage of patients with DTN <60 doubled from 32.4% to 70.3% (P<0.001). Patients with DTN ≤60 did not differ significantly with respect to demographics, comorbidities, or National Institutes of Health Stroke Scale score in comparison with those treated after 60 minutes. CONCLUSIONS: Door-to-CT and DTN times improved dramatically after applying 10 best practices, all of which were later incorporated into the Target Stroke Guidelines created by the American Heart Association. The only factor that significantly affected DTN60 was the intervention itself, indicating that these best practices can result in improved DTN times.

Time and diffusion lesion size in major anterior circulation ischemic strokes.

BACKGROUND AND PURPOSE: Major anterior circulation ischemic strokes caused by occlusion of the distal internal carotid artery or proximal middle cerebral artery or both account for about one third of ischemic strokes with mostly poor outcomes. These strokes are treatable by intravenous tissue-type plasminogen activator and endovascular methods. However, dynamics of infarct growth in these strokes are poorly documented. The purpose was to help understand infarct growth dynamics by measuring acute infarct size with diffusion-weighted imaging (DWI) at known times after stroke onset in patients with documented internal carotid artery/middle cerebral artery occlusions. METHODS: Retrospectively, we included 47 consecutive patients with documented internal carotid artery/middle cerebral artery occlusions who underwent DWI within 30 hours of stroke onset. Prospectively, 139 patients were identified using the same inclusion criteria. DWI lesion volumes were measured and correlated to time since stroke onset. Perfusion data were reviewed in those who underwent perfusion imaging. RESULTS: Acute infarct volumes ranged from 0.41 to 318.3 mL. Infarct size and time did not correlate (R2=0.001). The majority of patients had DWI lesions that were <25% the territory at risk (<70 mL) whether they were imaged <8 or >8 hours after stroke onset. DWI lesions corresponded to areas of greatly reduced perfusion. CONCLUSIONS: Poor correlation between infarct volume and time after stroke onset suggests that there are factors more powerful than time in determining infarct size within the first 30 hours. The observations suggest that highly variable cerebral perfusion via the collateral circulation may primarily determine infarct growth dynamics. If verified, clinical implications include the possibility of treating many patients outside traditional time windows.

Increased task-relevant fMRI responsiveness in comatose cardiac arrest patients is associated with improved neurologic outcomes.

Early prediction of the recovery of consciousness in comatose cardiac arrest patients remains challenging. We prospectively studied task-relevant fMRI responses in 19 comatose cardiac arrest patients and five healthy controls to assess the fMRI's utility for neuroprognostication. Tasks involved instrumental music listening, forward and backward language listening, and motor imagery. Task-specific reference images were created from group-level fMRI responses from the healthy controls. Dice scores measured the overlap of individual subject-level fMRI responses with the reference images. Task-relevant responsiveness index (Rindex) was calculated as the maximum Dice score across the four tasks. Correlation analyses showed that increased Dice scores were significantly associated with arousal recovery (P < 0.05) and emergence from the minimally conscious state (EMCS) by one year (P < 0.001) for all tasks except motor imagery. Greater Rindex was significantly correlated with improved arousal recovery (P = 0.002) and consciousness (P = 0.001). For patients who survived to discharge (n = 6), the Rindex's sensitivity was 75% for predicting EMCS (n = 4). Task-based fMRI holds promise for detecting covert consciousness in comatose cardiac arrest patients, but further studies are needed to confirm these findings. Caution is necessary when interpreting the absence of task-relevant fMRI responses as a surrogate for inevitable poor neurological prognosis.

Comparison of wideband steady-state free precession and T2-weighted fast spin echo in spine disorder assessment at 1.5 and 3 T.

Wideband steady-state free precession (WB-SSFP) is a modification of balanced steady-state free precession utilizing alternating repetition times to reduce susceptibility-induced balanced steady-state free precession limitations, allowing its use for high-resolution myelographic-contrast spinal imaging. Intertissue contrast and spatial resolution of complete-spine-coverage 3D WB-SSFP were compared with those of 2D T2-weighted fast spin echo, currently the standard for spine T2-imaging. Six normal subjects were imaged at 1.5 and 3 T. The signal-to-noise ratio efficiency (SNR per unit-time and unit-volume) of several tissues was measured, along with four intertissue contrast-to-noise ratios; nerve-ganglia:fat, intradural-nerves:cerebrospinal fluid, nerve-ganglia:muscle, and muscle:fat. Patients with degenerative and traumatic spine disorders were imaged at both MRI fields to demonstrate WB-SSFP clinical advantages and disadvantages. At 3 T, WB-SSFP provided spinal contrast-to-noise ratios 3.7-5.2 times that of fast spin echo. At 1.5 T, WB-SSFP contrast-to-noise ratio was 3-3.5 times that of fast spin echo, excluding a 1.7 ratio for intradural-nerves:cerebrospinal fluid. WB-SSFP signal-to-noise ratio efficiency was also higher. Three-dimensional WB-SSFP disadvantages relative to 2D fast spin echo are reduced edema hyperintensity, reduced muscle signal, and higher motion sensitivity. WB-SSFP's high resolution and contrast-to-noise ratio improved visualization of intradural nerve bundles, foraminal nerve roots, and extradural nerve bundles, improving detection of nerve compression in radiculopathy and spinal-stenosis. WB-SSFP's high resolution permitted reformatting into orthogonal planes, providing distinct advantages in gauging fine spine pathology.

Reliability of cerebral blood volume maps as a substitute for diffusion-weighted imaging in acute ischemic stroke.

PURPOSE: To assess the reliability of cerebral blood volume (CBV) maps as a substitute for diffusion-weighted MRI (DWI) in acute ischemic stroke. In acute stroke, DWI is often used to identify irreversibly injured "core" tissue. Some propose using perfusion imaging, specifically CBV maps, in place of DWI. We examined whether CBV maps can reliably subsitute for DWI, and assessed the effect of scan duration on calculated CBV. MATERIALS AND METHODS: We retrospectively identified 58 patients who underwent DWI and MR perfusion imaging within 12 h of stroke onset. CBV in each DWI lesion's center was divided by CBV in the normal-appearing contralateral hemisphere to yield relative regional CBV (rrCBV). The proportion of lesions with decreased rrCBV was calculated. After using the full scan duration (110 s after contrast injection), rrCBV was recalculated using simulated shorter scans. The effect of scan duration on rrCBV was tested with linear regression. RESULTS: Using the full scan duration (110 s), rrCBV was increased in most DWI lesions (62%; 95% confidence interval, 48-74%). rrCBV increased with increasing scan duration (P < 0.001). Even with the shortest duration (39.5 s) rrCBV was increased in 33% of lesions. CONCLUSION: Because DWI lesions may have elevated or decreased CBV, CBV maps cannot reliably substitute for DWI in identifying the infarct core.

Severe cerebral edema in substance-related cardiac arrest patients.

BACKGROUND: Studies of neurologic outcomes have found conflicting results regarding differences between patients with substance-related cardiac arrests (SRCA) and non-SRCA. We investigate the effects of SRCA on severe cerebral edema development, a neuroimaging intermediate endpoint for neurologic injury. METHODS: 327 out-of-hospital comatose cardiac arrest patients were retrospectively analyzed. Demographics and baseline clinical characteristics were examined. SRCA categorization was based on admission toxicology screens. Severe cerebral edema classification was based on radiology reports. Poor clinical outcomes were defined as discharge Cerebral Performance Category scores > 3. RESULTS: SRCA patients (N = 86) were younger (P < 0.001), and more likely to have non-shockable rhythms (P < 0.001), be unwitnessed (P < 0.001), lower Glasgow Coma Scale scores (P < 0.001), absent brainstem reflexes (P < 0.05) and develop severe cerebral edema (P < 0.001) than non-SRCA patients (N = 241). Multivariable analyses found younger age (P < 0.001), female sex (P = 0.008), non-shockable rhythm (P = 0.01) and SRCA (P = 0.05) to be predictors of severe cerebral edema development. Older age (P < 0.001), non-shockable rhythm (P = 0.02), severe cerebral edema (P < 0.001), and absent pupillary light reflexes (P = 0.004) were predictors of poor outcomes. SRCA patients had higher proportion of brain deaths (P < 0.001) compared to non-SRCA patients. CONCLUSIONS: SRCA results in higher rates of severe cerebral edema development and brain death. The absence of statistically significant differences in discharge outcomes or survival between SRCA and non-SRCA patients may be related to the higher rate of withdrawal of life-sustaining treatment (WLST) in the non-SRCA group. Future neuroprognostic studies may opt to include neuroimaging markers as intermediate measures of neurologic injury which are not influenced by WLST decisions.

Outcome in patients with H1N1 influenza and cerebrovascular injury treated with extracorporeal membrane oxygenation.

BACKGROUND: Although intracranial hemorrhage and infarction have been reported in patients with H1N1 influenza infection treated with extracorporeal membrane oxygenation (ECMO), the clinical outcomes of these patients are not well described. METHODS: The authors present two patients with H1N1 influenza infection and diffuse cerebrovascular injury in the setting of ECMO. RESULTS: Diffuse cerebrovascular injury including intraparenchymal hemorrhage was found on head CT and brain MRI in both cases and confirmed by autopsy in one patient who died. Punctate foci of susceptibility effect were seen in both patients on T2* susceptibility-weighted or susceptibility-sensitive gradient echo sequences. These foci of susceptibility effect were consistent with infarction on histopathologic evaluation in the patient who died. The other patient made an excellent clinical recovery. CONCLUSIONS: Frequent and early surveillance imaging should be obtained in patients with H1N1 influenza infection undergoing ECMO, although the presence of diffuse cerebral injury, including intraparenchymal hemorrhage and multifocal punctate susceptibility effect, does not necessarily portend a poor prognosis.

Early experience of translating pH-weighted MRI to image human subjects at 3 Tesla.

BACKGROUND AND PURPOSE: In acute stroke, mismatch between lesions seen on diffusion- (DWI) and perfusion-weighted (PWI) MRI has been used to identify ischemic tissue before irreversible damage. Nevertheless, the concept of PWI/DWI mismatch is oversimplified and the ischemic tissue metabolic status and outcome are often heterogeneous. Tissue pH, a well-regulated physiological index that alters on disrupted tissue metabolism, may provide a surrogate metabolic imaging marker that augments the DWI and PWI for penumbra imaging. METHODS: pH-weighted MRI was obtained by probing the pH-dependent amide proton transfer between endogenous mobile proteins/peptides and tissue water. The technique was validated using animal stroke models, optimized for human use, and preliminarily tested for imaging healthy volunteers. RESULTS: pH-weighted MRI is sensitive and specific to ischemic tissue acidosis. pH MRI can be optimized for clinical use, and a pilot human study showed it is feasible using a standard 3 Tesla MRI scanner. CONCLUSIONS: Ischemic acidosis can be imaged via an endogenous pH-weighted MRI technique, which complements conventional PWI and DWI for penumbra imaging. pH-weighted MRI has been optimized and appears feasible and practical in imaging human subjects. Additional study is necessary to elucidate the diagnostic use of pH MRI in stroke patients.

Combining acute diffusion-weighted imaging and mean transmit time lesion volumes with National Institutes of Health Stroke Scale Score improves the prediction of acute stroke outcome.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether acute diffusion-weighted imaging (DWI) and mean transit time (MTT) lesion volumes and presenting National Institutes of Health Stroke Scale (NIHSS) can identify patients with acute ischemic stroke who will have a high probability of good and poor outcomes. METHODS: Fifty-four patients with acute ischemic stroke who had MRI within 9 hours of symptom onset and 3-month follow-up with modified Rankin scale were evaluated. Acute DWI and MTT lesion volumes and baseline NIHSS scores were calculated. Clinical outcomes were considered good if the modified Rankin Scale was 0 to 2. RESULTS: The 33 of 54 (61%) patients with good outcomes had significantly smaller DWI lesion volumes (P=0.0001), smaller MTT lesion volumes (P<0.0001), and lower NIHSS scores (P<0.0001) compared with those with poor outcomes. Receiver operating characteristic curves for DWI, MTT, and NIHSS relative to poor outcome had areas under the curve of 0.889, 0.854, and 0.930, respectively, which were not significantly different. DWI and MTT lesion volumes predicted outcome better than mismatch volume or percentage mismatch. All patients with a DWI volume >72 mL (13 of 54) and an NIHSS score >20 (6 of 54) had poor outcomes. All patients with an MTT volume of <47 mL (16 of 54) and an NIHSS score <8 (17 of 54) had good outcomes. Combining clinical and imaging thresholds improved prognostic yield (70%) over clinical (43%) or imaging (54%) thresholds alone (P=0.01). CONCLUSIONS: Combining quantitative DWI and MTT with NIHSS predicts good and poor outcomes with high probability and is superior to NIHSS alone.

Existence of the diffusion-perfusion mismatch within 24 hours after onset of acute stroke: dependence on proximal arterial occlusion.

PURPOSE: To assess the existence of a mismatch between lesions on diffusion-weighted (DW) and perfusion-weighted (PW) magnetic resonance (MR) images obtained within 24 hours after onset of acute stroke and to use mismatch data and angiographic evidence of proximal arterial occlusion (PAO) to investigate whether the existence of the mismatch depends on the existence of PAO. MATERIALS AND METHODS: In this institutional review board-approved, HIPAA-compliant study, 109 retrospectively identified patients had undergone DW and PW imaging within 24 hours of stroke onset. Relative mismatch was computed as the difference between lesion volumes on mean transit time maps and DW images, divided by DW lesion volume. Computed tomographic (CT) angiography or MR angiography distinguished patients with PAO (n = 68) from those with no PAO (NPAO; n = 41). Eligibility for hypothetical thrombolysis was assessed with two different criteria: (a) one derived from the successful Desmoteplase in Acute Ischemic Stroke Trial (DIAS) and Dose Escalation of Desmoteplase for Acute Ischemic Stroke Trial (DEDAS), and (b) another requiring 160% mismatch. RESULTS: Of the 109 patients, 77 (71%) satisfied the DIAS-DEDAS eligibility criteria, and 61 (56%) satisfied the 160% criterion. The NPAO patients demonstrated decreasing eligibility with increasing time after onset by using DIAS-DEDAS criteria (P = .015) and showed a similar trend with the 160% criterion (P = .078). The NPAO patients were less likely to be eligible after 9 hours than before 9 hours (17% for >9 hours vs 72% for <9 hours with DIAS-DEDAS criteria, P = .002; and 8% for >9 hours vs 45% for <9 hours with 160% criterion, P = .033). However, PAO patients demonstrated a trend toward increasing eligibility with the DIAS-DEDAS criteria (P = .099) and no significant difference for after 9 hours versus before 9 hours (84% for >9 hours vs 78% for <9 hours with DIAS-DEDAS criteria, P = .742; and 68% for >9 hours vs 69% for <9 hours with 160% criterion, P > .999). CONCLUSION: Persistence of mismatch after 9 hours is common and occurs most often in patients with PAO.

Diffuse microvascular dysfunction and loss of white matter integrity predict poor outcomes in patients with acute ischemic stroke.

We sought to investigate the relationship between blood-brain barrier (BBB) permeability and microstructural white matter integrity, and their potential impact on long-term functional outcomes in patients with acute ischemic stroke (AIS). We studied 184 AIS subjects with perfusion-weighted MRI (PWI) performed <9 h from last known well time. White matter hyperintensity (WMH), acute infarct, and PWI-derived mean transit time lesion volumes were calculated. Mean BBB leakage rates (K2 coefficient) and mean diffusivity values were measured in contralesional normal-appearing white matter (NAWM). Plasma matrix metalloproteinase-2 (MMP-2) levels were studied at baseline and 48 h. Admission stroke severity was evaluated using the NIH Stroke Scale (NIHSS). Modified Rankin Scale (mRS) was obtained at 90-days post-stroke. We found that higher mean K2 and diffusivity values correlated with age, elevated baseline MMP-2 levels, greater NIHSS and worse 90-day mRS (all p < 0.05). In multivariable analysis, WMH volume was associated with mean K2 ( p = 0.0007) and diffusivity ( p = 0.006) values in contralesional NAWM. In summary, WMH severity measured on brain MRI of AIS patients is associated with metrics of increased BBB permeability and abnormal white matter microstructural integrity. In future studies, these MRI markers of diffuse cerebral microvascular dysfunction may improve prediction of cerebral tissue infarction and functional post-stroke outcomes.