Efficacy Assessment of Cerebral Perfusion Augmentation Through Functional Connectivity in an Acute Canine Stroke Model.

BACKGROUND AND PURPOSE: Ischemic stroke disrupts functional connectivity within the brain's resting-state networks (RSNs), impacting recovery. This study evaluates the effects of NEH (Norepinephrine and Hydralazine), a cerebral perfusion augmentation therapy, on RSN integrity in a hyper-acute canine stroke model. MATERIALS AND METHODS: Fifteen adult purpose-bred mongrel canines, divided into treatment and control (natural history) groups, underwent endovascular induction of acute middle cerebral artery occlusion (MCAO). Post-occlusion, the treatment group received intra-arterial Norepinephrine (0.1-1.52 µg/kg/min, adjusted for 25-45 mmHg above baseline mean arterial pressure) and Hydralazine (20mg). Resting-state fMRI data were acquired with a 3.0 T scanner using a BOLD-sensitive EPI sequence (TR/TE=1400 ms/20ms, 2.5 mm slices, 300 temporal positions). Preprocessing included motion correction, spatial smoothing (2.5 mm FWHM), and high-pass filtering (0.01 Hz cutoff). Functional connectivity within RSNs were analyzed through group-level independent component analysis (ICA) and weighted whole-brain ROI-to-ROI connectome, pre-and post-MCAO. RESULTS: NEH therapy significantly maintained connectivity post-MCAO in the Higher-order Visual and Parietal RSNs, as evidenced by thresholded statistical mapping (TFCE p-corr > 0.95). However, this preservation was network-dependent, with no significant changes in the Primary Visual and Sensorimotor networks. CONCLUSIONS: NEH demonstrates potential as a proof-of-concept therapy for maintaining RSN functional connectivity following ischemic stroke, emphasizing the therapeutic promise of perfusion augmentation. These insights reinforce the role of functional connectivity as a measurable endpoint for stroke intervention efficacy, suggesting clinical translatability for patients with insufficient collateral circulation. ABBREVIATIONS: NEH＝ Norepinephrine and Hydralazine; RSN＝ Resting-State Network; ICA = Independent Component Analysis; rsfMRI = resting-state Functional Magnetic Resonance Imaging; MCAO = Middle Cerebral Artery Occlusion; TFCE = Threshold-Free Cluster Enhancement.

Augmentation of perfusion with simultaneous vasodilator and inotropic agents in experimental acute middle cerebral artery occlusion: a pilot study.

BACKGROUND: This study tests the hypothesis that simultaneous cerebral blood pressure elevation and potent vasodilation augments perfusion to ischemic tissue in acute ischemic stroke and it varies by degree of pial collateral recruitment. METHODS: Fifteen mongrel canines were included. Subjects underwent permanent middle cerebral artery occlusion; pial collateral recruitment was scored before treatment. Seven treatment subjects received a continuous infusion of norepinephrine (0.1-1.52 µg/kg/min; titrated 25-45 mmHg above baseline mean arterial pressure while keeping systolic blood pressure below 180 mmHg) and hydralazine (20 mg) starting 30 min post-occlusion. Perfusion (cerebral blood flow-CBF) was evaluated with quantitative dynamic susceptibility contrast MRI 2.5 hours post-occlusion to produce images in mL/100 g/min, and relative CBF measured as ratios. Mean region of interest (ROI) values were reported, and compared and subject to regression analysis to elucidate trends. RESULTS: Differences in quantitative CBF (qCBF) between treatment and control group varied by degree of pial collateral recruitment, based on Wilcoxon rank sum scores and regression model fit. For poorly collateralized subjects, ipsilateral anatomic, core infarct, and penumbra regions showed treatment with higher qCBF, raised above the ischemic threshold, compared with the control, while well collateralized subjects showed a paradoxical decrease maintained above the ischemic threshold for neuronal death. qCBF on the contralateral side increased regardless of collateralization. CONCLUSION: Results suggest that perfusion can be augmented in ischemic stroke with norepinephrine and hydralazine. Perfusion augmentation depends on degree of collateralization and territory in question, with some evidence of vascular steal.

Effect of early Sanguinate (PEGylated carboxyhemoglobin bovine) infusion on cerebral blood flow to the ischemic core in experimental middle cerebral artery occlusion.

BACKGROUND: Sanguinate, a bovine PEGylated carboxyhemoglobin-based oxygen carrier with vasodilatory, oncotic and anti-inflammatory properties designed to release oxygen in hypoxic tissue, was tested to determine if it improves infarct volume, collateral recruitment and blood flow to the ischemic core in hyperacute middle cerebral artery occlusion (MCAO). METHODS: Under an IACUC approved protocol, 14 mongrel dogs underwent endovascular permanent MCAO. Seven received Sanguinate (8 mL/kg) intravenously over 10 min starting 30 min following MCAO and seven received a similar volume of normal saline. Relative cerebral blood flow (rCBF) was assessed using neutron-activated microspheres prior to MCAO, 30 min following MCAO and 30 min following intervention. Pial collateral recruitment was scored and measured by arterial arrival time (AAT) immediately prior to post-MCAO microsphere injection. Diffusion-weighted 3T MRI was used to assess infarct volume approximately 2 hours after MCAO. RESULTS: Mean infarct volumes for control and Sanguinate-treated subjects were 4739 mm3 and 2585 mm3 (p=0.0443; r2=0.687), respectively. Following intervention, rCBF values were 0.340 for controls and 0.715 in the Sanguinate group (r2=0.536; p=0.0064). Pial collateral scores improved only in Sanguinate-treated subjects and AAT decreased by a mean of 0.314 s in treated subjects and increased by a mean of 0.438 s in controls (p<0.0276). CONCLUSION: Preliminary results indicate that topload bolus administration of Sanguinate in hyperacute ischemic stroke significantly improves infarct volume, pial collateral recruitment and CBF in experimental MCAO immediately following its administration.

A Roadmap for Developing Plasma Diagnostic and Prognostic Biomarkers of Cerebral Cavernous Angioma With Symptomatic Hemorrhage (CASH).

BACKGROUND: Cerebral cavernous angioma (CA) is a capillary microangiopathy predisposing more than a million Americans to premature risk of brain hemorrhage. CA with recent symptomatic hemorrhage (SH), most likely to re-bleed with serious clinical sequelae, is the primary focus of therapeutic development. Signaling aberrations in CA include proliferative dysangiogenesis, blood-brain barrier hyperpermeability, inflammatory/immune processes, and anticoagulant vascular domain. Plasma levels of molecules reflecting these mechanisms and measures of vascular permeability and iron deposition on magnetic resonance imaging are biomarkers that have been correlated with CA hemorrhage. OBJECTIVE: To optimize these biomarkers to accurately diagnose cavernous angioma with symptomatic hemorrhage (CASH), prognosticate the risk of future SH, and monitor cases after a bleed and in response to therapy. METHODS: Additional candidate biomarkers, emerging from ongoing mechanistic and differential transcriptome studies, would further enhance the sensitivity and specificity of diagnosis and prediction of CASH. Integrative combinations of levels of plasma proteins and characteristic micro-ribonucleic acids may further strengthen biomarker associations. We will deploy advanced statistical and machine learning approaches for the integration of novel candidate biomarkers, rejecting noncorrelated candidates, and determining the best clustering and weighing of combined biomarker contributions. EXPECTED OUTCOMES: With the expertise of leading CA researchers, this project anticipates the development of future blood tests for the diagnosis and prediction of CASH to clinically advance towards precision medicine. DISCUSSION: The project tests a novel integrational approach of biomarker development in a mechanistically defined cerebrovascular disease with a relevant context of use, with an approach applicable to other neurological diseases with similar pathobiologic features.

Influence of simultaneous pressor and vasodilatory agents on the evolution of infarct growth in experimental acute middle cerebral artery occlusion.

BACKGROUND: This study sought to test the hypothesis that simultaneous central blood pressure elevation and potent vasodilation can mitigate pial collateral-dependent infarct growth in acute ischemic stroke. METHODS: Twenty mongrel canines (20-30 kg) underwent permanent middle cerebral artery occlusion (MCAO). Eight subjects received continuous infusion of norepinephrine (0.1-1.5200 µg/kg/min; titrated to a median of 34 mmHg above baseline mean arterial pressure) and hydralazine (20 mg) starting 30 min following MCAO. Pial collateral recruitment was scored prior to treatment and used to predict infarct volume based on a previously reported parameterization. Serial diffusion magnetic resonance imaging (MRI) acquisitions tracked infarct volumes over a 4-hour time frame. Infarct volumes and infarct volume growth between treatment and control groups were compared with each other and to predicted values. Fluid-attenuated inversion recovery (FLAIR) MRI, susceptibility weighted imaging (SWI), and necropsy findings were included in the evaluation. RESULTS: Differences between treatment and control group varied by pial collateral recruitment based on indicator-variable regression effects analysis with interaction confirmed by regression model fit. Benefit in treatment group was only in subjects with poor collaterals which had 35.7% less infarct volume growth (P=0.0008; ANOVA) relative to controls. Measured infarct growth was significantly lower than predicted by the model (linear regression partial F-test, slope P<0.001, intercept=0.003). There was no evidence for cerebral hemorrhage or posterior reversible encephalopathy syndrome. CONCLUSION: Our results indicate that a combination of norepinephrine and hydralazine administered in the acute phase of ischemic stroke mitigates infarct evolution in subjects with poor but not good collateral recruitment.

QSM in canine model of acute cerebral ischemia: A pilot study.

PURPOSE: In the present study, we investigated the potential of QSM to assess the physiological state of cortical tissue in the middle cerebral artery occlusion canine model of a cerebral ischemia. METHODS: Experiments were performed in 8 anesthetized canines. Gradient echo, perfusion, and DWI data of brains at normal and ischemic states were acquired. In the postprocessed susceptibility and quantitative cerebral blood flow maps, changes in values within the middle cerebral artery-fed cortical territories were quantified both on the ischemic and normal contralateral hemisphere side. RESULTS: QSM values in critically ischemic tissue were significantly different from contralateral values-namely, susceptibility increase was observed in the cases in which cerebral perfusion was maintained above the threshold of neuronal death. Furthermore, the data indicates presence of a significant correlation between the changes in susceptibility values, cerebral perfusion, and the infarct volume and pial collateral scores. Additionally, our data suggests that difference in cortical susceptibility is prospectively indicative of the infarct growth rate. CONCLUSION: In an experimental permanent middle cerebral artery occlusion model, QSM was shown to correlate with the functional parameters characterizing viability of ischemic tissue, thus warranting further research on its ability to provide complementary information during acute stroke MRI examinations in humans.

Common transcriptome, plasma molecules, and imaging signatures in the aging brain and a Mendelian neurovascular disease, cerebral cavernous malformation.

Brain senescence is associated with impaired endothelial barrier function, angiogenic and inflammatory activity, and propensity to brain hemorrhage. The same pathological changes occur in cerebral cavernous malformations (CCM), a genetic neurovascular anomaly. We hypothesized common transcriptomic and plasma cytokine signatures in the aging brain and CCM. We identified 320 genes [fold change ≥1.5; p < 0.05; false discovery rate (FDR) corrected] commonly dysregulated in the aging brain and CCM. Ontology and pathway analyses of the common differentially expressed genes were related to inflammation and extracellular matrix organization. Plasma levels of C-reactive protein and angiopoietin-2 were significantly greater in older compared to younger healthy non-CCM subjects and were also greater in CCM (Sporadic and Familial) subjects regardless of age (all: p < 0.05; FDR corrected). Plasma levels of vascular endothelial growth factor were significantly greater in older compared to younger subjects, in both healthy non-CCM and Sporadic-CCM groups (all: padj < 0.05). Plasma levels of vascular endothelial growth factor were also significantly greater in Familial-CCM cases with germ line mutations regardless of age (all: padj < 0.05) compared to both healthy non-CCM and Sporadic-CCM subjects. Brain white matter vascular permeability assessed by MRI followed the same pattern as vascular endothelial growth factor across all groups. In addition, quantitative susceptibility mapping of brain white matter, a measure of iron deposition, was increased in older compared to younger healthy non-CCM subjects. Genetic aberrations, plasma molecules, and imaging biomarkers in a well characterized Mendelian neurovascular disease may also be applicable in the aging brain. Graphical abstract.

Predictors for the extent of pial collateral recruitment in acute ischemic stroke.

BACKGROUND: Pial arterioles can provide a variable degree of collateral flow to ischemic vascular territories during acute ischemic stroke. This study sought to identify predictive factors of the degree of pial collateral recruitment in acute ischemic stroke. METHODS: Clinical information and arteriograms from 62 consecutive patients with stroke due to either middle cerebral artery (MCA) M1 segment or internal carotid artery (ICA) terminus occlusion within 6 h following symptom onset were retrospectively reviewed. Pial collaterals were defined based on the extent of reconstitution of the MCA territory. Patients with slow antegrade flow distal to the occlusion site were excluded and no anesthetics were used prior or during angiography. Results were analyzed using multivariate nominal logistic regression. RESULTS: Better pial collateral recruitment was associated with proximal MCA versus ICA terminus occlusion (p = 0.005; odds ratio (OR) = 9.3; 95% confidence interval (CI), 2.16-53.3), lower presenting National Institutes of Health Stroke Scale Score (NIHSSS) (p = 0.023; OR = 6.51; 95% CI, 1.49-41.7), and lower diastolic blood pressure (p = 0.0411; OR = 5.05; 95% CI, 1.20-29.2). Age, gender, symptom duration, diabetes, laterality, systolic blood pressure, glucose level, hematocrit, platelet level, and white blood cell count at presentation were not found to have a statistically significant association with pial collateral recruitment. CONCLUSIONS: Extent of pial collateral recruitment is strongly associated with the occlusion site (MCA M1 segment versus ICA terminus) and less strongly associated with presenting NIHSSS and diastolic blood pressure.

Absolute quantitative MR perfusion and comparison against stable-isotope microspheres.

PURPOSE: This work sought to compare a quantitative T1 bookend dynamic susceptibility contrast MRI based perfusion protocol for absolute cerebral blood flow (qCBF) against CBF measured by the stable-isotope neutron capture microsphere method, a recognized reference standard for measuring tissue blood flow, at normocapnia, hypercapnia, and in acute stroke. METHODS: CBF was measured in anesthetized female canines by MRI and microspheres over 2 consecutive days for each case. On day 1, 5 canines were measured before and during a physiological challenge induced by carbogen inhalation; on day 2, 4 canines were measured following permanent occlusion of the middle cerebral artery. CBF and cerebrovascular reactivity measured by MRI and microsphere deposition were compared. RESULTS: MRI correlated strongly with microspheres at the hemispheric level for CBF during normo- and hypercapnic states (r2 = 0.96), for individual cerebrovascular reactivity (r2 = 0.84), and for postocclusion CBF (r2 = 0.82). Correction for the delay and dispersion of the contrast bolus resulted in a significant improvement in the correlation between MRI and microsphere deposition in the ischemic state (r2 = 0.96). In all comparisons, moderate correlations were found at the regional level. CONCLUSION: In an experimental canine model with and without permanent occlusion of the middle cerebral artery, MRI-based qCBF yielded moderate to strong correlations for absolute quantitative CBF and cerebrovascular reactivity measurements during normocapnia and hypercapnia. Correction for delay and dispersion greatly improved the quantitation during occlusion of the middle cerebral artery, underscoring the importance for this correction under focal ischemic condition.

Atorvastatin Treatment of Cavernous Angiomas with Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial.

BACKGROUND: More than a million Americans harbor a cerebral cavernous angioma (CA), and those who suffer a prior symptomatic hemorrhage have an exceptionally high rebleeding risk. Preclinical studies show that atorvastatin blunts CA lesion development and hemorrhage through inhibiting RhoA kinase (ROCK), suggesting it may confer a therapeutic benefit. OBJECTIVE: To evaluate whether atorvastatin produces a difference compared to placebo in lesional iron deposition as assessed by quantitative susceptibility mapping (QSM) on magnetic resonance imaging in CAs that have demonstrated a symptomatic hemorrhage in the prior year. Secondary aims shall assess effects on vascular permeability, ROCK activity in peripheral leukocytes, signal effects on clinical outcomes, adverse events, and prespecified subgroups. METHODS: The phase I/IIa placebo-controlled, double-blinded, single-site clinical trial aims to enroll 80 subjects randomized 1-1 to atorvastatin (starting dose 80 mg PO daily) or placebo. Dosing shall continue for 24-mo or until reaching a safety endpoint. EXPECTED OUTCOMES: The trial is powered to detect an absolute difference of 20% in the mean percent change in lesional QSM per year (2-tailed, power 0.9, alpha 0.05). A decrease in QSM change would be a signal of potential benefit, and an increase would signal a safety concern with the drug. DISCUSSION: With firm mechanistic rationale, rigorous preclinical discoveries, and biomarker validations, the trial shall explore a proof of concept effect of a widely used repurposed drug in stabilizing CAs after a symptomatic hemorrhage. This will be the first clinical trial of a drug aimed at altering rebleeding in CA.

Fuzzy c-means segmentation of major vessels in angiographic images of stroke.

Patients suffering from ischemic stroke develop varying degrees of pial arterial supply (PAS), which can affect patient response to reperfusion therapy and risk of hemorrhage. Since vessel segmentation may be an important part in identifying PAS, we present a fuzzy c-means (FCM) clustering method to segment major vessels in x-ray angiograms. Our approach consists of semiautomatic region of interest (ROI) delineation, separation of major vessels from capillary blush and/or background noise through FCM clustering, and identification of the major vessel category. This method was applied to a database of x-ray angiograms of 24 patients acquired at various frame rates. The ground truth for performance evaluation was the designation by an expert radiologist selecting image pixels as being vessel or nonvessel. From receiver operating characteristic (ROC) analysis, area under the ROC curve (AUC) was the performance metric in the task of distinguishing between major vessels and blush or background. When clustering data into three categories and performing FCM segmentation on each ROI separately, the AUC was 0.89 for the entire database and [Formula: see text] for all examined frame-rates. In conclusion, our method showed promising performance in identifying major vessels and is anticipated to become an integral part of automatic quantification of PAS.

Quantitative susceptibility mapping as a monitoring biomarker in cerebral cavernous malformations with recent hemorrhage.

BACKGROUND: Quantitative Susceptibility Mapping (QSM) MRI allows accurate assessment of iron content in cerebral cavernous malformations (CCM), and a threshold increase by 6% in QSM has been shown to reflect new symptomatic hemorrhage (SH) in previously stable lesions. PURPOSE/HYPOTHESIS: It is unclear how lesional QSM evolves in CCMs after recent SH, and whether this could serve as a monitoring biomarker in clinical trials aimed at preventing rebleeding in these lesions. STUDY TYPE: This is a prospective observational cohort study. POPULATION: 16 CCM patients who experienced a SH within the past year, whose lesion was not resected or irradiated. FIELD STRENGTH/SEQUENCE: The data acquisition was performed using QSM sequence implemented on a 3T MRI system ASSESSMENT: The lesional QSM assessments at baseline and yearly during 22 patient-years of follow-up were performed by a trained research staff including imaging scientists. STATISTICAL TESTS: Biomarker changes were assessed in relation to clinical events. Clinical trial modeling was performed using two-tailed tests of time-averaged difference (assuming within-patient correlation of 0.8, power = 0.9 and alpha = 0.1) to detect 20%, 30% or 50% effects of intervention on clinical and biomarkers event rates during two years of follow-up. RESULTS: The change in mean lesional QSM of index hemorrhagic lesions was +7.93% per patient-year in the whole cohort. There were 5 cases (31%) of recurrent SH or lesional growth, and twice as many instances (62%) with a threshold (6%) increase in QSM. There were no instances of SH hemorrhage or lesional growth without an associated threshold increase in QSM during the same epoch. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;47:1133-1138.

Vascular permeability and iron deposition biomarkers in longitudinal follow-up of cerebral cavernous malformations.

OBJECTIVE Vascular permeability and iron leakage are central features of cerebral cavernous malformation (CCM) pathogenesis. The authors aimed to correlate prospective clinical behavior of CCM lesions with longitudinal changes in biomarkers of dynamic contrast-enhanced quantitative permeability (DCEQP) and quantitative susceptibility mapping (QSM) assessed by MRI. METHODS Forty-six patients with CCMs underwent 2 or more permeability and/or susceptibility studies in conjunction with baseline and follow-up imaging and clinical surveillance during a mean 12.05 months of follow-up (range 2.4-31.27 months). Based on clinical and imaging features, cases/lesions were classified as stable, unstable, or recovering. Associated and predictive changes in quantitative permeability and susceptibility were investigated. RESULTS Lesional mean permeability and QSM values were not significantly different in stable versus unstable lesions at baseline. Mean lesional permeability in unstable CCMs with lesional bleeding or growth increased significantly (+85.9% change; p = 0.005), while mean permeability in stable and recovering lesions did not significantly change. Mean lesional QSM values significantly increased in unstable lesions (+44.1% change; p = 0.01), decreased slightly with statistical significance in stable lesions (-3.2% change; p = 0.003), and did not significantly change in recovering lesions. Familial cases developing new lesions during the follow-up period showed a higher background brain permeability at baseline (p = 0.001), as well as higher regional permeability (p = 0.003) in the area that would later develop a new lesion as compared with the homologous contralateral brain region. CONCLUSIONS In vivo assessment of vascular permeability and iron deposition on MRI can serve as objective and quantifiable biomarkers of disease activity in CCMs. This may be applied in natural history studies and may help calibrate clinical trials. The 2 techniques are likely applicable in other disorders of vascular integrity and iron leakage such as aging, hemorrhagic microangiopathy, and traumatic brain injury.

Vascular permeability in cerebral cavernous malformations.

Patients with the familial form of cerebral cavernous malformations (CCMs) are haploinsufficient for the CCM1, CCM2, or CCM3 gene. Loss of corresponding CCM proteins increases RhoA kinase-mediated endothelial permeability in vitro, and in mouse brains in vivo. A prospective case-controlled observational study investigated whether the brains of human subjects with familial CCM show vascular hyperpermeability by dynamic contrast-enhanced quantitative perfusion magnetic resonance imaging, in comparison with CCM cases without familial disease, and whether lesional or brain vascular permeability correlates with CCM disease activity. Permeability in white matter far (WMF) from lesions was significantly greater in familial than in sporadic cases, but was similar in CCM lesions. Permeability in WMF increased with age in sporadic patients, but not in familial cases. Patients with more aggressive familial CCM disease had greater WMF permeability compared to those with milder disease phenotype, but similar lesion permeability. Subjects receiving statin medications for routine cardiovascular indications had a trend of lower WMF, but not lesion, permeability. This is the first demonstration of brain vascular hyperpermeability in humans with an autosomal dominant disease, as predicted mechanistically. Brain permeability, more than lesion permeability, may serve as a biomarker of CCM disease activity, and help calibrate potential drug therapy.

Acute spinal cord compression: CQI framework increases resource efficiency while promoting delivery of high-quality care.

PURPOSE: Literature reports indicate that advanced imaging is overutilized, especially in the emergency setting. At our institution, stat spinal MRI for suspected acute spinal cord compression (ASCC) was perceived to be excessively utilized. A continuous quality improvement process was employed to investigate this trend and improve the efficiency of this diagnosis. METHODS: Spine imaging in patients with suspected ASCC was retrospectively evaluated for appropriateness of indications and quality of imaging. Based on the results, a new institutional policy for ordering MR for suspected ASCC was implemented, concurrent with development of a new screening spine MRI protocol. Subsequently, indications, efficacy, and imaging utilization of the new strategy were analyzed for improved operational effectiveness. RESULTS: The initial retrospective study demonstrated only a 1.4% positive rate of ASCC as well as image-quality degradation due to patient motion resulting from prolonged scan times. Based on these results, a new institutional policy for ordering stat ASCC spine MRI was instituted with an updated screening MRI protocol. This policy resulted in a positive rate of ASCC of 4.4%, and decreased scan time by 50%-70%, while preserving diagnostic image quality and decreasing resource utilization. CONCLUSIONS: As suspected, stat spinal MRI for ASCC was excessively utilized at our institution. The study demonstrated that systemic improvements regarding this issue can be achieved by using a multidisciplinary approach and following a continuous quality improvement methodology. A new MRI protocol for identification of ASCC was found to preserve image quality and diagnostic confidence, while simultaneously decreasing scan time and use of valuable health care resources.

Adenoma localization for recurrent or persistent primary hyperparathyroidism using dynamic four-dimensional CT and venous sampling.

PURPOSE: To determine if parathyroid venous sampling (PVS) combined with four-dimensional (4D) computed tomography (CT) improves sensitivity and accuracy of identification of parathyroid adenoma in patients with recurrent or persistent primary hyperparathyroidism (pHPT) and negative technetium-99m methoxyisobutyl isonitrile ((99m)Tc-MIBI) and ultrasound (US) scans. MATERIALS AND METHODS: Both PVS and 4D CT were performed in 28 patients with recurrent or persistent pHPT and negative (99m)Tc-MIBI and US examinations. Localization by 4D CT alone and in combination with PVS and lateralization by PVS alone were retrospectively assessed for correlation with surgical results. Suspected adenomas on 4D CT were said to correlate with PVS if venous drainage identified on CT corresponded to sites of elevated parathyroid hormone concentration on PVS. Lesions difficult to identify on 4D CT were lesions < 1 cm in longest dimension. Results of 4D CT were classified as positive, negative, or equivocal. RESULTS: Surgery was performed in 22 of 28 patients. Surgery identified 23 parathyroid adenomas, 1 carcinoma, and 2 hyperplastic glands in 20 patients. 4D-CT alone localized 11 lesions in 10 patients. PVS helped localize 13 additional lesions in nine more patients and clarified two lesions that were equivocal on 4D CT. Comparing 4D CT alone with 4D CT plus PVS, the sensitivity increased from 50% to 95% (P = .004), and accuracy increased from 55% to 91% (P = .022). PVS lateralization had a sensitivity of 93.3%, positive predictive value of 66.7%, and accuracy of 63.6%. CONCLUSIONS: PVS significantly improves 4D CT localization of parathyroid adenomas in patients undergoing repeat surgery for pHPT with negative (99m)Tc-MIBI and US.

"Tumoral pseudoblush" identified within gliomas at high-spatial-resolution ultrahigh-field-strength gradient-echo MR imaging corresponds to microvascularity at stereotactic biopsy.

PURPOSE: To use directed biopsy sampling to determine whether microvascular assessment within gliomas, by means of ultrahigh-field-strength high-spatial-resolution gradient-echo (GRE) magnetic resonance (MR) imaging at 8 T, correlates with histopathologic assessment of microvascularity. MATERIALS AND METHODS: The study was institutional review board approved and HIPAA compliant. Informed consent was obtained. Thirty-five subjects with gliomas underwent 8-T and 80-cm MR imaging by using a GRE sequence (repetition time, 600-750 msec; echo time, 10 msec; in-plane resolution, 196 mm). Haphazardly arranged serpentine low-signal-intensity structures, often associated with areas of low signal intensity within the tumor bed ("tumoral pseudoblush") at MR imaging, were presumed to be related to tumoral microvascularity. Microvessel density (MVD) and microvessel size (MVS) ranked with a semiquantitative three-tier scale (high, medium, and low) relative to cortical penetrating veins were assessed from regions of interest identified at MR imaging and were compared with a similar assessment of stereotactic biopsy specimens by using Kendall τb. Tumor grade (high vs low) was compared with ultrahigh-field-strength high-resolution GRE MR analysis by using Pearson χ2. Discrepancies between 8-T and histopathologic assessment were identified and analyzed. RESULTS: Ultrahigh-field-strength high-resolution GRE MR imaging and histopathologic assessment concurred for MVS (P<.0001) and MVD (P<.0001). World Health Organization classification tumor grade was associated with number (P<.0005) and size (P<.0005) of foci of microvascularity within the tumor bed at 8-T MR imaging. Radiation-induced microvessel hyalinosis mimicked tumor microvascularity at 8-T MR imaging. Potential confounders could result from radiofrequency inhomogeneity and displaced normal microvasculature. CONCLUSION: Microvascularity identified as a tumoral pseudoblush at ultrahigh-field-strength high-resolution GRE MR imaging without contrast material shows promise as a marker for increased tumoral microvascularity.