Cerebral Blood Volume Maps Research Articles

Robust MR assessment of cerebral blood volume and mean vessel size using SPION-enhanced ultrashort echo acquisition

Intravascular superparamagnetic iron oxide nanoparticles (SPION)-enhanced MR transverse relaxation rates (∆R2⁎ and ∆R2) are widely used to investigate in vivo vascular parameters, such as the cerebral blood volume (CBV), microvascular volume (MVV), and mean vessel size index (mVSI, ∆R2⁎/∆R2). Although highly efficient, regional comparison of vascular parameters acquired using gradient-echo based ∆R2⁎ is hampered by its high sensitivity to magnetic field perturbations arising from air–tissue interfaces and large vessels. To minimize such demerits, we took advantage of the dual contrast property of SPION and both theoretically and experimentally verified the direct benefit of replacing gradient-echo based ∆R2⁎ measurement with ultra-short echo time (UTE)-based ∆R1 contrast to generate the robust CBV and mVSI maps. The UTE acquisition minimized the local measurement errors from susceptibility perturbations and enabled dose-independent CBV measurement using the vessel/tissue ∆R1 ratio, while independent spin-echo acquisition enabled simultaneous ∆R2 measurement and mVSI calculation of the cortex, cerebellum, and olfactory bulb, which are animal brain regions typified by significant susceptibility-associated measurement errors.

Quantification of serial changes in cerebral blood volume and metabolism in patients with recurrent glioblastoma undergoing antiangiogenic therapy

ObjectivesTo evaluate the usefulness of quantitative advanced magnetic resonance imaging (MRI) methods for assessment of antiangiogenic therapy (AAT) response in recurrent glioblastoma multiforme (GBM). MethodsEighteen patients with recurrent GBM received bevacizumab and 18 patients served as control group. Baseline MRI and two follow-up examinations were acquired every 3–5 months using dynamic susceptibility-weighted contrast (DSC) perfusion MRI and 1H-MR spectroscopic imaging (1H-MRSI). Maps of absolute cerebral blood volume (aCBV) were coregistered with choline (Cho) and N-acetyl-aspartate (NAA) concentrations and compared to usually used relative parameters as well as controls. ResultsPerfusion significantly decreased in responding and pseudoresponding GBMs but also in normal appearing brain after AAT onset. Cho and NAA concentrations were superior to Cr-ratios in lesion differentiation and showed a clear gap between responding and pseudoresponding lesions. Responders to AAT exceptionally frequently (6 out of 8 patients) showed remote GBM progression. ConclusionsQuantification of CBV reveals changes in normal brain perfusion due to AAT, which were not described so far. DSC perfusion MRI seems not to be suitable for differentiation between response and pseudoresponse to AAT. However, absolute quantification of brain metabolites may allow for distinction due to a clear gap at 6–9 months after therapy onset.

Abstract W P41: Multimodal Imaging ASPECTS: A Predictor Of Good Prognosis Before Thrombectomy

BACKGROUND: The goal of this study was to determine the accuracy and reliability of noncontrast CT (NCCT), perfusion CT parameters maps (CTP) an CT-angiography source images (CTASI), analyzed with ASPECTS (Alberta Stroke Program Early CT Scale), as final outcome predictors of endovascular stroke treatment. METHODS: Consecutive patients with ischemic stroke who received endovascular reperfusion were retrospectively analyzed (04/2009-06/2014). In acute stroke patients NCCT, CTP-CBV (maps of Cerebral Blood Volume) and CTASI was performed according to our hospital guidelines before thrombectomy. We independently applied the ASPECTS in all baselines NCCT, CBV-CTP, CTASI and follow-up NCCT 24H. Receiver-operating characteristic curve (ROC) analysis was performed to determine optimal thresholds for imaging parameters to predict dichotomized good clinical outcome (modified Rankin score ≤2, mRS). RESULTS: From a database containing 402 thrombectomies, 94 underwent CTP and CTA for acute cerebrovascular ischemia. Ninety-one with MCA or ICA occlusion were identified for our study (49% women, mean age 64+/-13 years; NIHSS at admission 17). Successful recanalization (TICI 2b-3) was achieved in 73/91 patients (80%). In ROC analysis higher CBV ASPECTS was associated with 90-day mRS score 0-2 (Area Under Curve=0.72;95% CI, 0.6-0.8; P:0.001) with optimal threshold of 8 (Sensivity 83%, Specificity 77%). The CTASI ASPECTS was highly correlated with 24h NCCT ASPECTS (r: 0.65;Spearman p:0.001). Favorable clinical outcomes (mRS 0-2) was greater in patients with CBV ASPECTS >8 compared with ≤8 (71% vs 37%;p:0.001) and CTACI ASPECTS>8 compared with ≤8 (68% vs 37%;p=0.02). In multivariate logistic regression CBV ASPECTS was associated with significant functional and radiological outcomes after adjustment for age, sex, time from CT to groin-puncture and baseline NIHSS (OR: 2.5; 95%CI:1.8-3.5, p:0.001). CONCLUSIONS: These results suggest that CBV ASPECTS approach can predict a favorable clinical outcome after endovascular treatment with good sensitivity and specificity. CTASI ASPECTS may be more sensitive for detection of infarction and more accurate for predicting the final infarct size however not to predict clinical outcome.

Acute ischemic stroke with tandem/terminal ICA occlusion - CT perfusion based case selection for mechanical recanalization

Rapid reperfusion in a patient with a favorable penumbral pattern is crucial to achieving a good outcome in acute ischemic stroke. Recanalization rates for tandem and terminal internal carotid artery (ICA) occlusion are better with endovascular management as compared with intravenous tissue plasminogen activator (IV-tPA) alone. We hypothesize that tissue-based selection would enable the identification of the ideal patient most suited for reperfusion therapy. We present our series of patients who developed tandem or terminal ICA occlusion and were selected for endovascular management based on their computed tomography (CT) perfusion (CTP) imaging. In this prospective study, 14 (29.16%) of the 48 patients treated by endovascular intervention between January 2011 and March 2014 had either tandem or terminal ICA occlusion. In the tandem group, thrombolysis in cerebral infarction (TICI) 2b/3 reperfusion and a good outcome was observed in five (71.42%, n = 7) and six patients (85.71%, n = 6), respectively. Among the terminal ICA occlusion group, TICI 2b/3 reperfusion and a good outcome was observed in three (42.8%, n = 7) and two patients (28.5%, n = 7), respectively. In patients with early reperfusion, a strong correlation with a median difference of one, in cerebral blood volume (CBV) Alberta Stroke Program Early CT Score (ASPECTS) on CBV map and post-procedure 24-h non-contrast CT, was noted. The median imaging-to-puncture and puncture-to -meaningful reperfusion time was 70 and 68.5 min, respectively, and, overall, good outcomes were seen in 57.1% of the patients. The cerebral blood volume (CBV) core estimation reliably predicted the final infarct volume. The key reasons for the significantly better outcomes seen in our cohort were the stringent perfusion imaging-based patient selection and the rapid reperfusion.

Impact of Severe Extracranial ICA Stenosis on MRI Perfusion and Diffusion Parameters in Acute Ischemic Stroke.

Purpose: The aim of this study was to investigate the impact of a coexisting internal carotid artery (ICA) stenosis on lesion volumes as well as diffusion and perfusion parameters in acute ischemic stroke resulting from middle cerebral artery (MCA) occlusion.Material and methods: Magnetic resonance imaging data of 32 patients with MCA occlusion with or without additional ICA stenosis imaged within 4.5 h of symptom onset were analyzed. Both groups consisted of 16 patients. Acute diffusion lesions were semi-automatically segmented in apparent diffusion coefficient (ADC) MRI datasets. Perfusion maps of cerebral blood volume (CBV), cerebral blood flow, mean transit time and Tmax were calculated using perfusion-weighted MRI datasets. Tissue-at-risk (TAR) volumes were generated by subtracting the ADC lesion from the hypoperfusion lesion defined by Tmax >6 s. Median ADC and perfusion parameter values were extracted separately for the diffusion lesion and TAR and used for statistical analysis.Results: No significant differences were found between the groups regarding the diffusion lesion and TAR volumes. Statistical analysis of diffusion and perfusion parameters revealed CBV as the only parameter with a significant difference (p = 0.009) contributing a small effect (η2 = 0.11) to the group comparison with higher CBV values for the patient group with a coexisting ICA stenosis, while no significant effects were found for the other diffusion and perfusion parameters analyzed.Conclusion: The results of this study suggest that a coexisting ICA stenosis does not have a strong effect on tissue status or perfusion parameters in acute stroke patients except for a moderate elevation of CBV. This may reflect improved collateral circulation or ischemic preconditioning in patients with a pre-existing proximal stenosis balancing impaired perfusion from the stenosis.

Delayed contrast extravasation MRI: a new paradigm in neuro-oncology.

Conventional magnetic resonance imaging (MRI) is unable to differentiate tumor/nontumor enhancing tissues. We have applied delayed-contrast MRI for calculating high resolution treatment response assessment maps (TRAMs) clearly differentiating tumor/nontumor tissues in brain tumor patients. One hundred and fifty patients with primary/metastatic tumors were recruited and scanned by delayed-contrast MRI and perfusion MRI. Of those, 47 patients underwent resection during their participation in the study. Region of interest/threshold analysis was performed on the TRAMs and on relative cerebral blood volume maps, and correlation with histology was studied. Relative cerebral blood volume was also assessed by the study neuroradiologist. Histological validation confirmed that regions of contrast agent clearance in the TRAMs >1 h post contrast injection represent active tumor, while regions of contrast accumulation represent nontumor tissues with 100% sensitivity and 92% positive predictive value to active tumor. Significant correlation was found between tumor burden in the TRAMs and histology in a subgroup of lesions resected en bloc (r(2) = 0.90, P < .0001). Relative cerebral blood volume yielded sensitivity/positive predictive values of 51%/96% and there was no correlation with tumor burden. The feasibility of applying the TRAMs for differentiating progression from treatment effects, depicting tumor within hemorrhages, and detecting residual tumor postsurgery is demonstrated. The TRAMs present a novel model-independent approach providing efficient separation between tumor/nontumor tissues by adding a short MRI scan >1 h post contrast injection. The methodology uses robust acquisition sequences, providing high resolution and easy to interpret maps with minimal sensitivity to susceptibility artifacts. The presented results provide histological validation of the TRAMs and demonstrate their potential contribution to the management of brain tumor patients.

NI-54 * HYPERVASCULAR VOLUME ESTIMATED BY COMPARISON TO A LARGE-SCALE CEREBRAL BLOOD VOLUME (CBV) RADIOGRAPHIC ATLAS PREDICTS SURVIVAL IN RECURRENT GLIOBLASTOMA TREATED WITH BEVACIZUMAB

Background: Dynamic susceptibility contrast (DSC)-MRI is a well-established perfusion MR imaging technique for estimating relative cerebral blood volume (CBV) in primary brain tumors; however, tumors localized to regions with naturally elevated perfusion, including cortical tissue and common vascular territories, make evaluation of tumor vascularity difficult to assess. In the current study, we have constructed a large-scale radiographic atlas of CBV to assess treatment response to bevacizumab in individual patients with recurrent glioblastoma. Methods: Z-score normalized CBV maps were registered to stereotactic atlas space in 450 patients with brain tumors. A CBV atlas was created by calculating the voxel-wise mean and variability in CBV. MRI and CBV maps from 32 recurrent glioblastoma patients were then obtained prior to and following treatment with bevacizumab, registered to and compared with the CBV atlas. The volume of tumor tissue with elevated CBV, percentage of enhancing tumor with elevated CBV, and the mean and maximum change in normalized CBV intensity relative to the atlas were computed. Results: Voxel-wise comparison of individual patient CBV maps to the atlas allowed delineation of elevated tumor perfusion from artery and normal cortical tissue. An atlas-defined hypervascular tumor blood volume greater than 2.35 cc prior to treatment, 0.14 cc after treatment, and a decrease in atlas-defined hypervascular tumor volume less than 80% following treatment were characteristic of a shorter PFS and OS. Traditional measures of CBV were not predictive of PFS or OS. Conclusions: This study highlights the advantages of large-scale population maps to identify abnormal biological tissues.

Ferumoxytol administration does not alter infarct volume or the inflammatory response to stroke in mice

Ferumoxytol is an ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle that is FDA-approved as an intravenous iron replacement therapy for the treatment of iron deficiency anemia in patients with chronic kidney disease. Ferumoxytol has also been used as a contrast agent for cerebral blood volume mapping by magnetic resonance imaging (MRI), which suggests it could be used for imaging hemodynamic abnormalities after stroke. However, circulating macrophages can internalize USPIOs, and recent data indicate that the accumulation of iron in macrophages can lead them to adopt the M1 pro-inflammatory phenotype. Therefore, the uptake of intravenously administered iron particles by circulating macrophages that home to the stroke core could potentially alter the inflammatory response to stroke. To test this possibility in vivo we administered a dose of ferumoxytol previously used to obtain cerebral blood volume maps in healthy humans by steady-state susceptibility contrast (SSC) MRI to BALB/cJ mice 48h after stroke and examined cytokine levels, microglial/macrophage activation, and lesion volume in the brain 5 days later. Treatment with ferumoxytol did not lead to any differences in these parameters. These data indicate that the use of ferumoxytol as a contrast agent for brain imaging after stroke does not alter the inflammatory response to stroke in mice, and is therefore unlikely to do so in human subjects.

Evaluation of the microenvironmental heterogeneity in high-grade gliomas with IDH1/2 gene mutation using histogram analysis of diffusion-weighted imaging and dynamic-susceptibility contrast perfusion imaging.

The purpose of our study was to explore the difference between isocitrate dehydrogenase (IDH)-1/2 gene mutation-positive and -negative high-grade gliomas (HGGs) using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps. We enrolled 52 patients with histopathologically confirmed HGGs with IDH1/2 (P) (n = 16) or IDH1/2 (N) (n = 36). Histogram parameters of ADC and nCBV maps were correlated with gene mutations by using the unpaired student's t test and multivariable stepwise logistic regression analysis. The mean ADC value was higher in the IDH1 (P) group than IDH1 (N) (1,282.8 vs. 1,159.6 mm(2)/s, P = .0113). In terms of the cumulative ADC histograms, the 10th and 50th percentile values were also higher in the IDH1 (P) than IDH1 (N) (P = .0104 and .0183, respectively). We observed a higher 90th percentile value (3.121 vs. 2.397, P = .0208) and a steeper slope between the 10th (C10) and 90th (C90) of cumulative nCBV histograms (0.03386 vs. 0.02425/%, P = .0067) in the IDH1 (N) group. Multivariate analysis showed that the mean ADC mean value (P = .0048), the C90 value (P = .0113), and the slope between C10 and C90 (P = .0049) were the significant variables in the differentiation of IDH1 (P) from IDH1 (N). In conclusion, histogram analysis of ADC and nCBV maps based on entire tumor volume can be a useful tool for distinguishing IDH1 (P) and IDH1 (N), and it predicts that IDH (P) tumors have a more heterogeneous microenvironment than IDH (N) ones.

Assessment of a combined spin- and gradient-echo (SAGE) DSC-MRI method for preclinical neuroimaging

The goal of this study was to optimize and validate a combined spin- and gradient-echo (SAGE) sequence for dynamic susceptibility-contrast magnetic resonance imaging to obtain hemodynamic parameters in a preclinical setting. The SAGE EPI sequence was applied in phantoms and in vivo rat brain (normal, tumor, and stroke tissue). Partial and full Fourier encoding schemes were implemented and characterized. Maps of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), vessel size index (VSI), volume transfer constant (Ktrans), and volume fraction of the extravascular extracellular space (ve) were obtained. Partial Fourier encoding provided shortened echo times with acceptable signal-to-noise ratio and temporal stability, thus enabling reliable characterization of T2, T2⁎ and T1 in both phantoms and rat brain. The hemodynamic parameters CBV, CBF, and MTT for gradient-echo and spin-echo contrast were determined in tumor and stroke; VSI, Ktrans, and ve were also computed in tumor tissue. The SAGE EPI sequence allows the acquisition of multiple gradient- and spin-echoes, from which measures of perfusion, permeability, and vessel size can be obtained in a preclinical setting. Partial Fourier encoding can be used to minimize SAGE echo times and reliably quantify dynamic T2 and T2⁎ changes. This acquisition provides a more comprehensive assessment of hemodynamic status in brain tissue with vascular and perfusion abnormalities.

Prognostic value of blood flow estimated by arterial spin labeling and dynamic susceptibility contrast-enhanced MR imaging in high-grade gliomas.

Several studies evaluated the predictive value of dynamic susceptibility contrast enhanced (DSC) imaging and arterial spin labeling (ASL) with regard to histological grade. Yet still less is known about their significance in terms of patients prognosis. Our purpose was to evaluate the agreement between them and the prognostic value of ASL- and DSC-CBF measurements for time-to-recurrence (TTR). Sixty nine cases of WHO Grade 3-4 gliomas underwent both DSC- and ASL-MRI. Normalized ASL and DSC-based cerebral blood flow (CBF) maps as well as DSC-derived cerebral blood volume maps (CBV) were analyzed. Wilcoxon test and Bland-Altman plot analysis were applied in order to compare DSC-rCBF and ASL-rCBF. Spearman's rank correlation coefficients were determined for all perfusion parameters. Receiver operating characteristic (ROC) curve and survival curve analyses were performed. The median values of ASL-rCBF, DSC-rCBF, and DSC-rCBV were 5.3, 6.9, and 8.0, respectively. There was neither significant correlation nor difference between ASL-rCBF and DSC-rCBF. Slight proportional bias was demonstrated in the Bland-Altman plot analysis of ASL-rCBF and DSC-rCBF values. Unlikely to DSC-rCBV, DSC- and ASL-based rCBF parameters demonstrated moderate sensitivity and specifitity for tumor recurrence but no statistical significance regarding their prognostic values for TTR in the Kaplan-Meier analysis. There were neither correlation nor interchangeability between the DSC-rCBF and ASL-rCBF estimations, which demonstrated comparable, though not significant prognostic value for the prediction of TTR. rCBV measurements seem to provide the best sensitivity and specificity to predict tumor recurrence and survival time in these patients.

Contralateral dissociation between neural activity and cerebral blood volume during recurrent acute focal neocortical seizures.

ObjectiveWhether epileptic events disrupt normal neurovascular coupling mechanisms locally or remotely is unclear. We sought to investigate neurovascular coupling in an acute model of focal neocortical epilepsy, both within the seizure onset zone and in contralateral homotopic cortex.MethodsNeurovascular coupling in both ipsilateral and contralateral vibrissal cortices of the urethane-anesthetized rat were examined during recurrent 4-aminopyridine (4-AP, 15 mm, 1 μl) induced focal seizures. Local field potential (LFP) and multiunit spiking activity (MUA) were recorded via two bilaterally implanted 16-channel microelectrodes. Concurrent two-dimensional optical imaging spectroscopy was used to produce spatiotemporal maps of cerebral blood volume (CBV).ResultsRecurrent acute seizures in right vibrissal cortex (RVC) produced robust ipsilateral increases in LFP and MUA activity, most prominently in layer 5, that were nonlinearly correlated to local increases in CBV. In contrast, contralateral left vibrissal cortex (LVC) exhibited relatively smaller nonlaminar specific increases in neural activity coupled with a decrease in CBV, suggestive of dissociation between neural and hemodynamic responses.SignificanceThese findings provide insights into the impact of epileptic events on the neurovascular unit, and have important implications both for the interpretation of perfusion-based imaging signals in the disorder and understanding the widespread effects of epilepsy.

The Value of syngo DynaPBV Neuro During Neuro-Interventional Hypotensive Balloon Occlusion Test.

This study explored the value of flat detector computed tomography based brain perfusion imaging in assessing patient's tolerance prior to the permanent internal carotid artery occlusion. Ten patients diagnosed with neurovascular diseases through digital subtracted angiography (DSA) were enrolled into this study. Temporary balloon occlusion test (BOT) was performed for each patient with hypotensive challenge. During the test, parametric color-coded quantitative DSA (CCQ-DSA) was generated to evaluate the venous filling symmetry on both hemispheres. In addition, cerebral blood volume (CBV) maps were acquired before and during the test. Regions of interests were defined to quantitatively extract CBV value from affected and unaffected hemispheres and calculate relative CBV (rCBV), indicating perfusion symmetry. All the patients showed good perfusion symmetry before the test with rCBV close to 1.00. During the test, good perfusion symmetry was detected in 7 patients with averaged rCBV 1.03 ± 0.06. Only short venous delay and no ischemic complications were recognized. One patient had neither neurologic deficits nor long venous delay detected, however, showed hyper-perfusion in specific regions in the CBV maps. Two patients failed to pass the test, which showed significantly low CBV value from the affected hemisphere with maximum rCBV reduction close to 45%. CBV map had in general good consistency with clinical manifestations as well as venous filling in the BOT. Besides, it may provide further evidence of hemodynamic variations and delayed ischemic complications, and thus, had a potential to reduce risks and increase treatment safety.

Differentiation between vasogenic-edema versus tumor-infiltrative area in patients with glioblastoma during bevacizumab therapy: A longitudinal MRI study

BackgroundTreatment with bevacizumab is associated with substantial radiologic response in patients with glioblastoma (GB). However, following this initial response, changes in T2-weighted MRI signal may develop, suggesting an infiltrative pattern of tumor progression. The aim of this study was to differentiate between vasogenic-edema versus tumor-infiltrative area in GB patients. Methods and materialsFourteen patients with GB were longitudinally scanned, before and during intravenous bevacizumab therapy (5/10mg/kg every 2-weeks). A total of 40 MR scans including conventional, diffusion, dynamic susceptibility contrast, dynamic contrast enhancement imaging, and MR-spectroscopy (MRS) were analyzed. Classification of non-enhancing fluid-attenuation-inversion-recovery (FLAIR) area was performed based on mean diffusivity, cerebral blood volume and flow maps, and further characterized using multiple MRI parameters. ResultsThe non-enhancing FLAIR lesion area was classified into: vasogenic-edema, characterized by reduced perfusion and increased FLAIR values; or tumor-infiltrative area, characterized by increased perfusion. Tumor-infiltrative area demonstrated a higher malignant pattern on MRS compared to areas of vasogenic-edema. Substantial reductions of the enhanced T1-weighted (58±10%) and hyperintense FLAIR (53±9%) lesion volumes were detected mainly during the first weeks of therapy, with a shift to an infiltrative pattern of tumor progression thereafter, as detected by an increase in tumor-infiltrative area in the majority of patients, which correlated with progression-free survival (week 8: r=−0.86, p=0.003, week 16: r=−0.99, p=0.001). ConclusionCharacterization of non-enhancing hyperintense FLAIR lesion area in GB patients can provide an MR-based biomarker, indicating a shift to an infiltrative progression pattern, and may improve therapy response assessment in patients following bevacizumab therapy.

Crossed Cerebellar Diaschisis in Acute Isolated Thalamic Infarction Detected by Dynamic Susceptibility Contrast Perfusion MRI

PurposeCrossed cerebellar diaschisis (CCD) is a state of neural depression caused by loss of connections to injured neural structures remote from the cerebellum usually evaluated by positron emission tomography. Recently it has been shown that dynamic susceptibility contrast perfusion weighted MRI (PWI) may also be feasible to detect the phenomenon. In this study we aimed to assess the frequency of CCD on PWI in patients with acute thalamic infarction.MethodsFrom a MRI report database we identified patients with acute isolated thalamic infarction. Contralateral cerebellar hypoperfusion was identified by inspection of time to peak (TTP) maps and evaluated quantitatively on TTP, mean transit time (MTT), cerebral blood flow and volume (CBF, CBV) maps. A competing cerebellar pathology or an underlying vascular pathology were excluded.ResultsA total of 39 patients was included. Common symptoms were hemiparesis (53.8%), hemihypaesthesia (38.5%), dysarthria (30.8%), aphasia (17.9%), and ataxia (15.4%). In 9 patients (23.1%) PWI showed hypoperfusion in the contralateral cerebellar hemisphere. All of these had lesions in the territory of the tuberothalamic, paramedian, or inferolateral arteries. Dysarthria was observed more frequently in patients with CCD (6/9 vs. 6/30; OR 8.00; 95%CI 1.54–41.64, p = 0.01). In patients with CCD, the median ischemic lesion volume on DWI (0.91 cm3, IQR 0.49–1.54 cm3) was larger compared to patients with unremarkable PWI (0.51 cm3, IQR 0.32–0.74, p = 0.05). The most pronounced changes were found in CBF (0.94±0.11) and MTT (1.06±0.13) signal ratios, followed by TTP (1.05±0.02).ConclusionsMultimodal MRI demonstrates CCD in about 20% of acute isolated thalamic infarction patients. Lesion size seems to be a relevant factor in its pathophysiology.

Abstract W P32: Association of Low Cerebral Blood Volume With Negative FLAIR Hyperintensity in Acute Ischemic Stroke

Objective: FLAIR hyperintensity is being used in clinical trials as a surrogate imaging biomarker for stroke onset time to test the safety of thrombolysis. Studies have shown that patients with negative and positive FLAIR hyperintensity overlap at similar time points from stroke onset in the early phase of acute ischemic stroke (AIS). Hyperintensity on FLAIR MRI likely represents increased tissue water content. We sought to determine if cerebral blood volume (CBV) mediates FLAIR hyperintensity in the early phase of AIS. Methods: AIS patients seen in 2012 were included in the study if i) onset time was known, ii) an MRI with perfusion was performed within 12 hours of onset time, iii) had imaging confirmed vascular occlusion of ICA, M1, or M2. Following co-registration of raw perfusion images with FLAIR, CBV maps were generated using PMA ASIST™ software. Two raters blinded to clinical information separately evaluated the DWI, FLAIR and CBV maps and measured the signal intensity ratio (SIR) for the brightest region on FLAIR normalized by homologous contra-lateral tissue. The SIR was similarly measured for CBV in same region. FLAIR negative was defined as SIR&lt;1.15, “Low CBV” was defined as CBV SIR &lt;0.5. Results: One hundred eighty two patients were screened and 30 met all study criteria; 21 women, with mean age of 71 (± 16) years and median NIHSS 18 (IQR 9-22). Using linear regression analysis, CBV SIR was associated with FLAIR SIR (p &lt;0.049). In the 0-3hr time window, overall CBV was not associated with FLAIR hyperintensity. However, in the 3-7.5hr time window, patients with negative FLAIR were more likely to have low CBV and conversely, patients with positive FLAIR were more likely to have normal CBV. Conclusion: CBV likely mediates FLAIR hyperintensity in 3-7.5hr of stroke onset but it has less impact on FLAIR hyperintensity in the first 3 hours of AIS. Low CBV could be a potential surrogate imaging biomarker in addition to FLAIR hyperintensity in the early phase of AIS.

Reliability of CT Perfusion in the Evaluation of the Ischaemic Penumbra

CT perfusion (CTP) is part of the initial evaluation of stroke patients, allowing differentiation between infarcted tissue and the ischaemic penumbra and helping in the selection of patients for endovascular treatment. This study assessed the reliability of the qualitative evaluation CTP maps in defining the ischemic penumbra and identified potential pitfalls associated with this technique. We reviewed CTP scans of 45 consecutive patients admitted to our institution with anterior circulation acute ischaemic stroke. Two neuroradiologists performed qualitative evaluations of cerebral blood volume (CBV) and mean transit time (MTT) maps, using 24h follow-up non-contrast CT as surrogate marker for the area of definitive infarct. For each slice analyzed, the area of qualitative alteration in the CBV and MTT maps was classified as either being inferior, equal or superior to the area of infarct on the follow-up CT. Three out of 45 (7%) patients had admission CT CBV abnormalities larger than follow-up lesions; 34/45 (76%) patients had infarct areas smaller than initial MTT prolongation. In the group of patients with no recanalization 12/19 (63%) had infarct areas smaller than initial MTT lesion. CBV abnormality is a reliable marker for an irreversible ischaemic lesion, although rarely it may overestimate the ischaemic "core", possibly due to delay in contrast arrival to the brain. In the majority of patients without recanalization, MTT overestimated final infarct areas, probably because it does not differentiate true "at risk" penumbra from benign oligaemia. Qualitative evaluation of CBV and MTT maps may overestimate the real ischaemic penumbra.

Cerebral Blood Flow is an Earlier Indicator of Perfusion Abnormalities than Cerebral Blood Volume in Alzheimer's Disease

The purpose of this study was to elucidate whether cerebral blood flow (CBF) can better characterize perfusion abnormalities in predementia stages of Alzheimer's disease (AD) than cerebral blood volume (CBV) and whether cortical atrophy is more associated with decreased CBV or with decreased CBF. We compared measurements of CBV, CBF, and mean cortical thickness obtained from magnetic resonance images in a group of healthy controls, patients with mild cognitive impairment (MCI) who converted to AD after 2 years of clinical follow-up (MCI-c), and patients with mild AD. A significant decrease in perfusion was detected in the parietal lobes of the MCI-c patients with CBF parametric maps but not with CBV maps. In the MCI-c group, a negative correlation between CBF values and cortical thickness in the right parahippocampal gyrus suggests an increase in CBF that depends on cortical atrophy in predementia stages of AD. Our study also suggests that CBF deficits appear before CBV deficits in the progression of AD, as CBV abnormalities were only detected at the AD stage, whereas CBF changes were already detected in the MCI stage. These results confirm the hypothesis that CBF is a more sensitive parameter than CBV for perfusion abnormalities in MCI-c patients.

Increased hippocampal CA1 cerebral blood volume in schizophrenia.

Hippocampal hyperactivity has been proposed as a biomarker in schizophrenia. However, there is a debate whether the CA1 or the CA2/3 subfield is selectively affected. We studied 15 schizophrenia patients and 15 matched healthy control subjects with 3T steady state, gadolinium-enhanced, absolute cerebral blood volume (CBV) maps, perpendicular to the long axis of the hippocampus. The subfields of the hippocampal formation (subiculum, CA1, CA2/3, and hilus/dentate gyrus) were manually segmented to establish CBV values. Comparing anterior CA1 and CA2/3 CBV between patients and controls revealed a significant subfield-by-diagnosis interaction. This interaction was due to the combined effect of a trend of increased CA1 CBV (p = .06) and non-significantly decreased CA2/3 CBV (p = 0.14) in patients relative to healthy controls. These results support the emerging hypothesis of increased hippocampal activity as a biomarker of schizophrenia and highlight the importance of subfield-level investigations.

Feasibility Study of Perfusion Imaging Using Flat Detector CT with an Intra-Arterial Injection Protocol Compared to Conventional Multi-Slice Perfusion CT with an Intravenous Injection Protocol

This study investigated the feasibility of using intra-arterial injection-based cerebral blood volume (CBV) imaging with flat detector computed tomography (CT, IAFD-CBV). It is proven that this new method could provide comparable physiologic information as standard intravenous injection-based multi-slice computed tomography CBV imaging (IVCT-CBV). Twelve patients were examined using both IAFD-CBV and IVCT-CBV. An experienced neuroradiologist read both sets of generated CBV maps. If a physiologic perfusion disorder was detected in standard IVCT-CBV, the focus was to check whether IAFD-CBV indicated the same disorder or not. Otherwise, if no disorder was detected, relative CBV (rCBV) values at different basal ganglia regions were measured for both CBV maps and then compared. For three patients with lesions, IAFD-CBV and IVCT-CBV showed similar perfusion disorders in the corresponding regions. For nine patients without lesions, both CBV maps showed good symmetry of contrast agent (CA) distribution for left/right hemisphere, the total average of rCBV was found to be 0.94 -/+0.18 and 1.01 -/+0.14 (1.0 for perfect symmetry) in IAFD-CBV and IVCT-CBV, respectively. However, compared to IVCT-CBV, IAFD-CBV imaging required 70% less contrast agent (CA). In general, a good correlation between IAFD-CBV and IVCT-CBV was found for all 12 patients. Minor deviations of IAFD-CBV were only detected at regions supplied by the middle cerebral artery. IAFD-CBV imaging, which can be directly performed in a catheterization laboratory, was proven to be technically feasible for real-time CBV assessment of the whole brain with good accuracy, and minimized CA usage.