Dynamic CTA-Derived Perfusion Maps Predict Final Infarct Volume: The Simple Perfusion Reconstruction Algorithm.

BACKGROUND AND PURPOSE: Infarct core volume measurement using CTP (CT perfusion) is a mainstay paradigm for stroke treatment decision-making. Yet, there are several downfalls with cine CTP technology that can be overcome by adopting the simple perfusion reconstruction algorithm (SPIRAL) derived from multiphase CTA. We compare SPIRAL with CTP parameters for the prediction of 24-hour infarction. MATERIALS AND METHODS: Seventy-two patients had admission NCCT, multiphase CTA, CTP, and 24-hour DWI. All patients had successful/quality reperfusion. Patient-level and cohort-level receiver operator characteristic curves were generated to determine accuracy. A 10-fold cross-validation was performed on the cohort-level data. Infarct core volume was compared for SPIRAL, CTP-time-to-maximum, and final DWI by Bland-Altman analysis. RESULTS: When we compared the accuracy in patients with early and late reperfusion for cortical GM and WM, there was no significant difference at the patient level (0.83 versus 0.84, respectively), cohort level (0.82 versus 0.81, respectively), or the cross-validation (0.77 versus 0.74, respectively). In the patient-level receiver operating characteristic analysis, the SPIRAL map had a slightly higher, though nonsignificant (P < .05), average receiver operating characteristic area under the curve (cortical GM/WM, r = 0.82; basal ganglia = 0.79, respectively) than both the CTP-time-to-maximum (cortical GM/WM = 0.82; basal ganglia = 0.78, respectively) and CTP-CBF (cortical GM/WM = 0.74; basal ganglia = 0.78, respectively) parameter maps. The same relationship was observed at the cohort level. The Bland-Altman plot limits of agreement for SPIRAL and time-to-maximum infarct volume were similar compared with 24-hour DWI. CONCLUSIONS: We have shown that perfusion maps generated from a temporally sampled helical CTA are an accurate surrogate for infarct core.

Impact of Ischemic Lesion Location on the mRS Score in Patients with Ischemic Stroke: A Voxel-Based Approach.

BACKGROUND AND PURPOSE: Previous studies indicated that ischemic lesion volume might be a useful surrogate marker for functional outcome in ischemic stroke but should be considered in the context of lesion location. In contrast to previous studies using the ROI approach, which has several drawbacks, the present study aimed to measure the impact of ischemic lesion location on functional outcome using a more precise voxelwise approach. MATERIALS AND METHODS: Datasets of patients with acute ischemic strokes from the Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands (MR CLEAN) were used. Primary outcome was functional outcome as assessed by the modified Rankin Scale 3 months after stroke. Ischemic lesion volume was determined on CT scans 3-9 days after stroke. Voxel-based lesion-symptom mapping techniques, including covariates that are known to be associated with functional outcome, were used to determine the impact of ischemic lesion location for outcome. RESULTS: Of the 500 patients in the MR CLEAN trial, 216 were included for analysis. The mean age was 63 years. Lesion-symptom mapping with inclusion of covariates revealed that especially left-hemispheric lesions in the deep periventricular white matter and adjacent internal capsule showed a great influence on functional outcome. CONCLUSIONS: Our study confirms that infarct location has an important impact on functional outcome of patients with stroke and should be considered in prediction models. After we adjusted for covariates, the left-hemispheric corticosubcortical fiber tracts seemed to be of higher functional importance compared with cortical lesions.

Brain Diffusion Abnormalities in Children with Tension-Type and Migraine-Type Headaches.

BACKGROUND AND PURPOSE: Tension-type and migraine-type headaches are the most common chronic paroxysmal disorders of childhood. The goal of this study was to compare regional cerebral volumes and diffusion in tension-type and migraine-type headaches against published controls. MATERIALS AND METHODS: Patients evaluated for tension-type or migraine-type headache without aura from May 2014 to July 2016 in a single center were retrospectively reviewed. Thirty-two patients with tension-type headache and 23 with migraine-type headache at an average of 4 months after diagnosis were enrolled. All patients underwent DWI at 3T before the start of pharmacotherapy. Using atlas-based DWI analysis, we determined regional volumetric and diffusion properties in the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, brain stem, and cerebral white matter. Multivariate analysis of covariance was used to test for differences between controls and patients with tension-type and migraine-type headaches. RESULTS: There were no significant differences in regional brain volumes between the groups. Patients with tension-type and migraine-type headaches showed significantly increased ADC in the hippocampus and brain stem compared with controls. Additionally, only patients with migraine-type headache showed significantly increased ADC in the thalamus and a trend toward increased ADC in the amygdala compared with controls. CONCLUSIONS: This study identifies early cerebral diffusion changes in patients with tension-type and migraine-type headaches compared with controls. The hypothesized mechanisms of nociception in migraine-type and tension-type headaches may explain the findings as a precursor to structural changes seen in adult patients with chronic headache.

Diffusion Tensor Imaging of White Matter in Children Born from Preeclamptic Gestations.

BACKGROUND AND PURPOSE: Individuals born from pregnancies complicated by preeclampsia have an elevated risk for cognitive impairment. Deviations in maternal plasma angiokines occur for prolonged intervals before clinical signs of preeclampsia. We hypothesized that fetal brain vascular and nervous tissue development become deviated during maternal progression toward preeclampsia and that such deviations would be detectable by MR imaging. MATERIALS AND METHODS: In this pilot study, 10 matched (gestational and current ages) pairs (5 boys/5 girls, 7-10 years of age) from preeclampsia or control pregnancies were examined by using diffusion tensor MR imaging. An unbiased voxel-based analysis was conducted on fractional anisotropy and mean diffusivity parametric maps. Six brain ROIs were identified for subsequent analysis by tractography (middle occipital gyrus, caudate nucleus and precuneus, cerebellum, superior longitudinal fasciculus, and cingulate gyrus). RESULTS: Statistical differences were present between groups for fractional anisotropy in the caudate nucleus (offspring from preeclamptic gestation > controls), volume of the tract for the superior longitudinal fasciculus (offspring from preeclamptic gestation > controls) and the caudate nucleus (offspring from preeclamptic gestation > controls), and for parallel diffusivity of the cingulate gyrus (offspring from preeclamptic gestation > controls). CONCLUSIONS: These novel preliminary results along with previous results from the same children that identified altered cerebral vessel calibers and increased regional brain volumes justify fully powered MR imaging studies to address the impact of preeclampsia on human fetal brain development.

Gray Matter Growth Is Accompanied by Increasing Blood Flow and Decreasing Apparent Diffusion Coefficient during Childhood.

BACKGROUND AND PURPOSE: Normal values of gray matter volume, cerebral blood flow, and water diffusion have not been established for healthy children. We sought to determine reference values for age-dependent changes of these parameters in healthy children. MATERIALS AND METHODS: We retrospectively reviewed MR imaging data from 100 healthy children. Using an atlas-based approach, age-related normal values for regional CBF, apparent diffusion coefficient, and volume were determined for the cerebral cortex, hippocampus, thalamus, caudate, putamen, globus pallidus, amygdala, and nucleus accumbens. RESULTS: All gray matter structures grew rapidly before the age of 10 years and then plateaued or slightly declined thereafter. The ADC of all structures decreased with age, with the most rapid changes occurring prior to the age of 5 years. With the exception of the globus pallidus, CBF increased rather linearly with age. CONCLUSIONS: Normal brain gray matter is characterized by rapid early volume growth and increasing CBF with concomitantly decreasing ADC. The extracted reference data that combine CBF and ADC parameters during brain growth may provide a useful resource when assessing pathologic changes in children.

Brain Structural and Vascular Anatomy Is Altered in Offspring of Pre-Eclamptic Pregnancies: A Pilot Study.

BACKGROUND AND PURPOSE: Pre-eclampsia is a serious clinical gestational disorder occurring in 3%-5% of all human pregnancies and characterized by endothelial dysfunction and vascular complications. Offspring born of pre-eclamptic pregnancies are reported to exhibit deficits in cognitive function, higher incidence of depression, and increased susceptibility to stroke. However, no brain imaging reports exist on these offspring. We aimed to assess brain structural and vascular anatomy in 7- to 10-year-old offspring of pre-eclamptic pregnancies compared with matched controls. MATERIALS AND METHODS: Offspring of pre-eclamptic pregnancies and matched controls (n = 10 per group) were recruited from an established longitudinal cohort examining the effects of pre-eclampsia. Children underwent MR imaging to identify brain structural and vascular anatomic differences. Maternal plasma samples collected at birth were assayed for angiogenic factors by enzyme-linked immunosorbent assay. RESULTS: Offspring of pre-eclamptic pregnancies exhibited enlarged brain regional volumes of the cerebellum, temporal lobe, brain stem, and right and left amygdalae. These offspring displayed reduced cerebral vessel radii in the occipital and parietal lobes. Enzyme-linked immunosorbent assay analysis revealed underexpression of the placental growth factor among the maternal plasma samples from women who experienced pre-eclampsia. CONCLUSIONS: This study is the first to report brain structural and vascular anatomic alterations in the population of offspring of pre-eclamptic pregnancies. Brain structural alterations shared similarities with those seen in autism. Vascular alterations may have preceded these structural alterations. This pilot study requires further validation with a larger population to provide stronger estimates of brain structural and vascular outcomes among the offspring of pre-eclamptic pregnancies.

Aneurysm Recurrence Volumetry Is More Sensitive than Visual Evaluation of Aneurysm Recurrences.

PURPOSE: Considerable inter-observer variability in the visual assessment of aneurysm recurrences limits its use as an outcome parameter evaluating new coil generations. The purpose of this study was to compare visual assessment of aneurysm recurrences and aneurysm recurrence volumetry with an example dataset of HydroSoft coils (HSC) versus bare platinum coils (BPC). METHODS: For this retrospective study, 3-dimensional time-of-flight magnetic resonance angiography datasets acquired 6 and 12 months after endovascular therapy using BPC only or mainly HSC were analyzed. Aneurysm recurrence volumes were visually rated by two observersas well as quantified by subtraction of the datasets after intensity-based rigid registration. RESULTS: A total of 297 aneurysms were analyzed (BPC: 169, HSC: 128). Recurrences were detected by aneurysm recurrence volumetry in 9 of 128 (7.0 %) treated with HSC and in 24 of 169 (14.2 %) treated with BPC (odds ratio: 2.39, 95 % confidence interval: 1.05-5.48; P = 0.039). Aneurysm recurrence volumetry revealed an excellent correlation between observers (Cronbach's alpha = 0.93). In contrast, no significant difference in aneurysm recurrence was found for visual assessment (3.9 % in HSC cases and 4.7 % in BPC cases). Recurrences were observed in aneurysms smaller than the sample median in 10 of 33 (30.3 %) by aneurysm recurrence volumetry and in 1 of 13 (7.7 %) by visual assessment. CONCLUSIONS: Aneurysm recurrences were detected more frequently by aneurysm recurrence volumetry when compared with visual assessment. By using aneurysm recurrence volumetry, differences between treatment groups were detected with higher sensitivity and inter-observer validity probably because of the higher detection rate of recurrences in small aneurysms.

Automatic differentiation of placental perfusion compartments by time-to-peak analysis in mice.

INTRODUCTION: The aim of this study was to develop an automatic differentiation of two perfusion compartments within the mouse placenta based on times of maximal contrast enhancement for a detailed and reproducible perfusion assessment. METHODS: Placentas (n = 17) from pregnant BALB/c mice (n = 10) were examined in vivo at 7T on gestation day 16.5. Coronal dual-echo 3D T1-weighted gradient-echo sequences were acquired after application of contrast agent for dynamic MRI. An adapted gamma variate function was fitted to the discrete concentration time curves to evaluate the effect of noise on perfusion and segmentation results. Time-to-peak maps based on fitted and discrete curves of each placenta were used to classify each voxel into the high- or low-blood flow compartment using k-means clustering. Perfusion analysis was performed using the steepest slope model and also applied to fitted and discrete curves. Results were compared to manually defined compartments from two independent observers using the Dice coefficient D. RESULTS: Manually defined placental areas of high-flow and low-flow were similar to the automatic segmentation for discrete (D = 0.76/0.75; D = 0.76/0.79) and fitted (D = 0.80/0.80; D = 0.81/0.82) concentration time curves. Mean perfusion values of discrete and fitted curves ranged in the high-flow compartment from 134 to 142 ml/min/100 ml (discrete) vs. 138-143 ml/min/100 ml (fitted) and in the low-flow compartment from 91 to 94 ml/min/100 ml (discrete) vs. 74-82 ml/min/100 ml (fitted). DISCUSSION: Our novel approach allows the automatic differentiation of perfusion compartments of the mouse placenta. The approach may overcome limitations of placental perfusion analyses caused by tissue heterogeneity and a potentially biased selection of regions of interest.

Prediction of infarction and reperfusion in stroke by flow- and volume-weighted collateral signal in MR angiography.

BACKGROUND AND PURPOSE: In proximal anterior circulation occlusive strokes, collateral flow is essential for good outcome. Collateralized vessel intensity in TOF- and contrast-enhanced MRA is variable due to different acquisition methods. Our purpose was to quantify collateral supply by using flow-weighted signal in TOF-MRA and blood volume-weighted signal in contrast-enhanced MRA to determine each predictive contribution to tissue infarction and reperfusion. MATERIALS AND METHODS: Consecutively (2009-2013), 44 stroke patients with acute proximal anterior circulation occlusion met the inclusion criteria with TOF- and contrast-enhanced MRA and penumbral imaging. Collateralized vessels in the ischemic hemisphere were assessed by TOF- and contrast-enhanced MRA using 2 methods: 1) visual 3-point collateral scoring, and 2) collateral signal quantification by an arterial atlas-based collateral index. Collateral measures were tested by receiver operating characteristic curve and logistic regression against 2 imaging end points of tissue-outcome: final infarct volume and percentage of penumbra saved. RESULTS: Visual collateral scores on contrast-enhanced MRA but not TOF were significantly higher in patients with good outcome. Visual collateral scoring on contrast-enhanced MRA was the best rater-based discriminator for final infarct volume < 90 mL (area under the curve, 0.81; P < .01) and percentage of penumbra saved >50% (area under the curve, 0.67; P = .04). Atlas-based collateral index of contrast-enhanced MRA was the overall best independent discriminator for final infarct volume of <90 mL (area under the curve, 0.94; P < .01). Atlas-based collateral index combining the signal of TOF- and contrast-enhanced MRA was the overall best discriminator for effective reperfusion (percentage of penumbra saved >50%; area under the curve, 0.89; P < .001). CONCLUSIONS: Visual scoring of contrast-enhanced but not TOF-MRA is a reliable predictor of infarct outcome in stroke patients with proximal arterial occlusion. By atlas-based collateral assessment, TOF- and contrast-enhanced MRA both contain predictive signal information for penumbral reperfusion. This could improve risk stratification in further studies.

ANTONIA perfusion and stroke. A software tool for the multi-purpose analysis of MR perfusion-weighted datasets and quantitative ischemic stroke assessment.

OBJECTIVES: The objective of this work is to present the software tool ANTONIA, which has been developed to facilitate a quantitative analysis of perfusion-weighted MRI (PWI) datasets in general as well as the subsequent multi-parametric analysis of additional datasets for the specific purpose of acute ischemic stroke patient dataset evaluation. METHODS: Three different methods for the analysis of DSC or DCE PWI datasets are currently implemented in ANTONIA, which can be case-specifically selected based on the study protocol. These methods comprise a curve fitting method as well as a deconvolution-based and deconvolution-free method integrating a previously defined arterial input function. The perfusion analysis is extended for the purpose of acute ischemic stroke analysis by additional methods that enable an automatic atlas-based selection of the arterial input function, an analysis of the perfusion-diffusion and DWI-FLAIR mismatch as well as segmentation-based volumetric analyses. RESULTS: For reliability evaluation, the described software tool was used by two observers for quantitative analysis of 15 datasets from acute ischemic stroke patients to extract the acute lesion core volume, FLAIR ratio, perfusion-diffusion mismatch volume with manually as well as automatically selected arterial input functions, and follow-up lesion volume. The results of this evaluation revealed that the described software tool leads to highly reproducible results for all parameters if the automatic arterial input function selection method is used. CONCLUSION: Due to the broad selection of processing methods that are available in the software tool, ANTONIA is especially helpful to support image-based perfusion and acute ischemic stroke research projects.

A statistical cerebroarterial atlas derived from 700 MRA datasets.

OBJECTIVES: The cerebroarterial system is a complex network of arteries that supply the brain cells with vitally important nutrients and oxygen. The inter-individual differences of the cerebral arteries, especially at a finer level, are still not understood sufficiently. The aim of this work is to present a statistical cerebroarterial atlas that can be used to overcome this problem. METHODS: Overall, 700 Time-of-Flight (TOF) magnetic resonance angiography (MRA) datasets of healthy subjects were used for atlas generation. Therefore, the cerebral arteries were automatically segmented in each dataset and used for a quantification of the vessel diameters. After this, each TOF MRA dataset as well as the corresponding vessel segmentation and vessel diameter dataset were registered to the MNI brain atlas. Finally, the registered datasets were used to calculate a statistical cerebroarterial atlas that incorporates information about the average TOF intensity, probability for a vessel occurrence and mean vessel diameter for each voxel. RESULTS: Visual analysis revealed that arteries with a diameter as small as 0.5 mm are well represented in the atlas with quantitative values that are within range of anatomical reference values. Moreover, a highly significant strong positive correlation between the vessel diameter and occurrence probability was found. Furthermore, it was shown that an intensity-based automatic segmentation of cerebral vessels can be considerable improved by incorporating the atlas information leading to results within the range of the inter-observer agreement. CONCLUSION: The presented cerebroarterial atlas seems useful for improving the understanding about normal variations of cerebral arteries, initialization of cerebrovascular segmentation methods and may even lay the foundation for a reliable quantification of subtle morphological vascular changes.

Application of the steepest slope model reveals different perfusion territories within the mouse placenta.

OBJECTIVES: The steepest slope model is a numerically robust and fast method for perfusion quantification. The purpose of this study was to evaluate if the steepest slope model can be used for quantifying placental perfusion in mice based on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) datasets. MATERIAL AND METHODS: T1-weighted DCE MRI was performed in 5 pregnant BALB/c mice on gestation day (gd) 14.5 and in 5 mice on gd 16.5 using a 7T small animal MRI scanner. The placentas were manually delineated in the DCE datasets and the arterial input function (AIF) was selected from the kidney hilus. Placental perfusion was determined on a voxel-by-voxel basis using the steepest slope model. Perfusion was averaged over the entire placenta as well as separately calculated for the high-flow compartment within the central labyrinth zone and for the remaining low-flow placenta tissue. The AIF selection was independently performed by two observers for assessment of inter-observer differences. RESULTS: Mean perfusion on gd 14.5 was 135 ml/min/100 ml (standard deviation SD: 29 ml/min/100 ml placenta) and 112 ml/min/100 ml on gd 16.5 for the whole placenta (SD: 32 ml/min/100 ml). Perfusion in the high flow compartment in the central labyrinth was significantly higher (p ≤ 0.002) than in the low-flow compartment including the remaining placenta tissue: 184 ml/min/100 ml (SD: 39 ml/min/100 ml) vs. 119 ml/min/100 ml (SD 28 ml/min/100 ml) on gd 14.5 and 158 ml/min/100 ml (SD: 58 ml/min/100 ml) vs. 114 ml/min/100 ml (SD: 52 ml/min/100 ml of placenta) on gd 16.5. The mean relative inter-rater observer difference was 6%. CONCLUSION: The steepest slope model is a computationally simple method, which allows perfusion quantification in the mouse placenta. Furthermore, the results of this work indicate that the different placental compartments should be analyzed separately to prevent biased results due to averaging.

Automated volumes-of-interest identification for classical and atypical Parkinsonian syndrome differentiation using T2' MR imaging.

OBJECTIVES: In clinical routine, patients with classical Parkinsonian syndromes (CPS) need to be differentiated from those with atypical Parkinsonian syndromes (APS), particularly with respect to prognosis and treatment decision. To date, this diagnosis is mainly based on clinical criteria, leading to failure rates up to 25%, motivating the development of image-based decision support systems. Magnetic resonance imaging (MRI) and in particular T2´ image sequences have been suggested as a potential marker for differential diagnosis. The aim of this study was to investigate whether automatically identified T2´ volumes-of-interest (VOIs) can be used for an automatic differentiation of CPS and APS patients. MATERIAL AND METHODS: 74 MRI datasets were available for this hypothesis generating trial, including image sequences from 24 healthy subjects, 33 CPS and 17 APS patients. First, a problem-specific reference atlas was generated using the healthy control datasets. Next, patients' datasets were registered to the atlas. Voxel-wise t-tests, reflecting significance levels of T2´ value differences between CPS and APS patients, were then applied for calculation of a p-map. Finally, the calculated p-map was thresholded and a connected component analysis was performed for final VOI detection. In parallel, manually defined VOIs were determined in grey and white matter for comparison. RESULTS: Three VOIs in parts of the basal ganglia and the left occipital lobe were automatically identified by the presented method. There was a trend for higher area under the curve on multivariable receiver operating characteristic curves for automatically determined VOIs over manually defined VOIs (0.939 vs. 0.818, p = 0.0572). CONCLUSION: The diagnostic role of automatically defined VOIs in differentiation of CPS and APS patients based on T2´ image sequences should be further investigated.

Comparison of 10 TTP and Tmax estimation techniques for MR perfusion-diffusion mismatch quantification in acute stroke.

BACKGROUND AND PURPOSE: The mismatch between lesions identified in perfusion- and diffusion-weighted MR imaging is typically used to identify tissue at risk of infarction in acute stroke. The purpose of this study was to analyze the variability of mismatch volumes resulting from different time-to-peak or time-to-maximum estimation techniques used for hypoperfused tissue definition. MATERIALS AND METHODS: Data of 50 patients with middle cerebral artery stroke and intracranial vessel occlusion imaged within 6 hours of symptom onset were analyzed. Therefore, 10 different TTP/Tmax techniques and delay thresholds between +2 and +12 seconds were used for calculation of perfusion lesions. Diffusion lesions were semiautomatically segmented and used for mismatch quantification after registration. RESULTS: Mean volumetric differences up to 40 and 100 mL in individual patients were found between the mismatch volumes calculated by the 10 TTP/Tmax estimation techniques for typically used delay thresholds. The application of typical criteria for the identification of patients with a clinically relevant mismatch volume resulted in different mismatch classifications in ≤24% of all cases, depending on the TTP/Tmax estimation method used. CONCLUSIONS: High variations of tissue-at-risk volumes have to be expected when using different TTP/Tmax estimation techniques. An adaption of different techniques by using correction formulas may enable more comparable study results until a standard has been established by agreement.

Comparison of 3D computer-aided with manual cerebral aneurysm measurements in different imaging modalities.

INTRODUCTION: To compare intra- and inter-observer reliability of aneurysm measurements obtained by a 3D computer-aided technique with standard manual aneurysm measurements in different imaging modalities. METHODS: A total of 21 patients with 29 cerebral aneurysms were studied. All patients underwent digital subtraction angiography (DSA), contrast-enhanced (CE-MRA) and time-of-flight magnetic resonance angiography (TOF-MRA). Aneurysm neck and depth diameters were manually measured by two observers in each modality. Additionally, semi-automatic computer-aided diameter measurements were performed using 3D vessel surface models derived from CE- (CE-com) and TOF-MRA (TOF-com) datasets. Bland-Altman analysis (BA) and intra-class correlation coefficient (ICC) were used to evaluate intra- and inter-observer agreement. RESULTS: BA revealed the narrowest relative limits of intra- and inter-observer agreement for aneurysm neck and depth diameters obtained by TOF-com (ranging between ±5.3 % and ±28.3 %) and CE-com (ranging between ±23.3 % and ±38.1 %). Direct measurements in DSA, TOF-MRA and CE-MRA showed considerably wider limits of agreement. The highest ICCs were observed for TOF-com and CE-com (ICC values, 0.92 or higher for intra- as well as inter-observer reliability). CONCLUSION: Computer-aided aneurysm measurement in 3D offers improved intra- and inter-observer reliability and a reproducible parameter extraction, which may be used in clinical routine and as objective surrogate end-points in clinical trials.

Quantitative t2 measurements in juvenile and late infantile neuronal ceroid lipofuscinosis.

PURPOSE: The two most prevalent forms of neuronal ceroid lipofuscinosis (NCL) are the juvenile form (Batten disease, CLN3) and late infantile form (Jansky-Bielschowsky disease, CLN2). The aim of this study was to compare quantitative T2-values of brain tissue in CLN2 and CLN3 patients with reference values from age-matched normal subjects. METHODS: Twenty-three CLN2 (n = 6) and CLN3 (n = 17) patients (m:f = 11:12) underwent MRI examination including a multiecho T2 sequence. Quantitative T2-values were measured in six defined regions of interest (ROIs) in the calculated quantitative T2 maps within the white matter (WM) and gray matter (GM). The extracted quantitative T2-values were compared with reference values from healthy children and young adults. Informed consent was obtained from the patients or their parents for all patients. RESULTS: Statistical analysis revealed elevated quantitative T2-values in nearly all ROIs placed in the WM of the CLN2 patients. In contrast to this finding, no significant differences were found for the quantitative T2-values of the CLN3 patients compared to the age-matched healthy controls in any of the defined WM ROIs. Both groups exhibited no significant alterations of the quantitative T2-values in the GM ROIs compared to the healthy subjects. CONCLUSION: Alterations of quantitative T2-values in the cerebral WM may not be a reliable sign to confirm the diagnosis in CLN3 patients but could prove valuable for diagnosis confirmation, follow-up examinations, and longitudinal monitoring of the disease progression in CLN2 patients.

Intranidal signal distribution in post-contrast time-of-flight MRA is associated with rupture risk factors in arteriovenous malformations.

PURPOSE: To evaluate if arteriovenous malformations (AVMs) that are associated with a high rupture risk (HRR) are represented by different intranidal Time-of-Flight (TOF) magnetic resonance angiography intensity distributions compared to those with presumably low rupture risk (LRR). METHODS: Fifty post-contrast TOF datasets of patients with an AVM were analyzed in this study. The patients were classified to the HRR group in case of a deep location, presence of exclusive deep venous drainage, previous hemorrhagic event or a combination thereof. For each TOF dataset, the AVM nidus was semi-automatically delineated and used for histogram extraction. Each histogram was analyzed by calculating the skewness, kurtosis, mean and median intensity and full-width-half-maximum. Statistical analysis was performed using parameter-wise two-sided t-tests of the parameters between the two groups. RESULTS: Based on morphological analysis, 21 patients were classified to the HRR and 29 patients to the LRR group. Statistical analysis revealed that TOF intensity distributions of HRR AVMs exhibit a significant higher skewness (p=0.0005) parameter compared to LRR AVMs. Contrary to these findings, no significant differences were found for the other parameters evaluated. CONCLUSION: Intranidal flow heterogeneity, for example, caused by turbulent flow conditions, may play an important role for risk of a hemorrhage. An analysis of post-contrast TOF intensities within the nidus of an AVM may offer simple and valuable information for clinical risk estimation of AVMs and needs to be tested prospectively.

Impact of protein content on proton diffusibility in intracranial cysts.

PURPOSE: The physical background of diffusion phenomena in intracranial cysts is unclear in some cases. To evaluate a potential dependency of proton diffusion on the concentration of proteins in cystic lesions we investigated the correlation of diffusion weighted imaging (DWI) and magnetization transfer ratio imaging (MTR) in intracranial cystic pathologies in vivo and in vitro with protein solutions. MATERIALS AND METHODS: 21 patients (14 male/7 female) with intracranial cystic lesions underwent preoperative MRI (1.5T) including MTR and DWI sequences. For comparison a series of samples with declining concentration of albumin was investigated in vitro with a 7T animal scanner. RESULTS: In the patients examination mean ADC values were 1.93×10-3mm2/sec and mean MTR values were 0.2. Mean ADC value of the albumin solutions was 0.22× 0-3mm2/sec and mean MTR was 0.12. ADC and MTR values showed a strong negative correlation in the patients (Spearman's rank correlation rs=-0.80, p<0.01) and a very strong negative correlation in the in vitro examinations (rs=-1.0, p<0.01). CONCLUSION: The strong negative correlation of ADC and MTR values suggest a strong influence of proteins on proton diffusion in intracranial cysts. The phenomena can be explained by macromolecules that bind nearby protons in their vicinity.

Classification of cerebral arteriovenous malformations and intranidal flow patterns by color-encoded 4D-hybrid-MRA.

BACKGROUND AND PURPOSE: 4D MRA has been evolving as a noninvasive supplement for DSA. The purpose of this study was to evaluate the feasibility of a newly developed blood flow visualization technique for the classification of cerebral AVMs. We hypothesized that 4D-hMRA allows detection of different flow patterns within the nidus as well as differentiation of feeders and draining veins and has very good agreement with DSA regarding the Spetzler-Martin grade. MATERIALS AND METHODS: Thirty-one consecutive patients with AVMs were evaluated by using 4D-hMRA and DSA by 2 blinded raters. Rating criteria included Spetzler-Martin score and other morphologic variables together with a new scale for 3 intranidal flow patterns (homogeneous = 1, unidirectional = 2, heterogeneous = 3). RESULTS: The Spetzler-Martin grades were rated different from DSA in 5 cases by rater 1 and in 3 cases by rater 2 with an excellent interrater reliability of κ = 0.96 (4/31, 1 by size and 3 by drainage). Each reader missed 5 feeders on 4D-hMRA. Draining veins were distinguished in the temporal course in 7 on DSA but in 8 and 12 on 4D-hybrid-MRA (raters 1 and 2 respectively), with κ = 0.79. A type 1 intranidal flow pattern was recognizable in 9 (30%) patients; type 2, in 19 (60%); and type 3, in 3 (10%). CONCLUSIONS: 4D-hMRA allows reliable Spetzler-Martin grading and detection of brain arteriovenous malformation feeding arteries and draining veins, with the drawback that for small vessels DSA is still needed. Draining veins might even be detected with higher sensitivity than on DSA. Discrimination of different intranidal flow patterns is possible, but their relevance for hemorrhage risk assessment and therapy planning requires further study.

Automatic correction of gaps in cerebrovascular segmentations extracted from 3D time-of-flight MRA datasets.

OBJECTIVES: Exact cerebrovascular segmentations are required for several applications in today's clinical routine. A major drawback of typical automatic segmentation methods is the occurrence of gaps within the segmentation. These gaps are typically located at small vessel structures exhibiting low intensities. Manual correction is very time-consuming and not suitable in clinical practice. This work presents a post-processing method for the automatic detection and closing of gaps in cerebrovascular segmentations. METHODS: In this approach, the 3D centerline is calculated from an available vessel segmentation, which enables the detection of corresponding vessel endpoints. These endpoints are then used to detect possible connections to other 3D centerline voxels with a graph-based approach. After consistency check, reasonable detected paths are expanded to the vessel boundaries using a level set approach and combined with the initial segmentation. RESULTS: For evaluation purposes, 100 gaps were artificially inserted at non-branching vessels and bifurcations in manual cerebrovascular segmentations derived from ten Time-of-Flight magnetic resonance angiography datasets. The results show that the presented method is capable of detecting 82% of the non-branching vessel gaps and 84% of the bifurcation gaps. The level set segmentation expands the detected connections with 0.42 mm accuracy compared to the initial segmentations. A further evaluation based on 10 real automatic segmentations from the same datasets shows that the proposed method detects 35 additional connections in average per dataset, whereas 92.7% were rated as correct by a medical expert. CONCLUSION: The presented approach can considerably improve the accuracy of cerebrovascular segmentations and of following analysis outcomes.