Epileptogenic Tubers Are Associated with Increased Kurtosis of Susceptibility Values: A Combined Quantitative Susceptibility Mapping and Stereoelectroencephalography Pilot Study.

BACKGROUND AND PURPOSE: Prior studies have found an association between calcification and the epileptogenicity of tubers in tuberous sclerosis complex. Quantitative susceptibility mapping is a novel tool sensitive to magnetic susceptibility alterations due to tissue calcification. We assessed the utility of quantitative susceptibility mapping in identifying putative epileptogenic tubers in tuberous sclerosis complex using stereoelectroencephalography data as ground truth. MATERIALS AND METHODS: We studied patients with tuberous sclerosis complex undergoing stereoelectroencephalography at a single center who had multiecho gradient-echo sequences available. Quantitative susceptibility mapping and R2* values were extracted for all tubers on the basis of manually drawn 3D ROIs using T1- and T2-FLAIR sequences. Characteristics of quantitative susceptibility mapping and R2* distributions from implanted tubers were compared using binary logistic generalized estimating equation models designed to identify ictal (involved in seizure onset) and interictal (persistent interictal epileptiform activity) tubers. These models were then applied to the unimplanted tubers to identify potential ictal and interictal tubers that were not sampled by stereoelectroencephalography. RESULTS: A total of 146 tubers were identified in 10 patients, 76 of which were sampled using stereoelectroencephalography. Increased kurtosis of the tuber quantitative susceptibility mapping values was associated with epileptogenicity (P = .04 for the ictal group and P = .005 for the interictal group) by the generalized estimating equation model. Both groups had poor sensitivity (35.0% and 44.1%, respectively) but high specificity (94.6% and 78.6%, respectively). CONCLUSIONS: Our finding of increased kurtosis of quantitative susceptibility mapping values (heavy-tailed distribution) was highly specific, suggesting that it may be a useful biomarker to identify putative epileptogenic tubers in tuberous sclerosis complex. This finding motivates the investigation of underlying tuber mineralization and other properties driving kurtosis changes in quantitative susceptibility mapping values.

Natural history of MRI brain volumes in patients with neuronal ceroid lipofuscinosis 3: a sensitive imaging biomarker.

PURPOSE: Grey matter (GM) atrophy due to neuronal loss is a striking feature of patients with CLN3 disease. A precise and quantitative description of disease progression is needed in order to establish an evaluation tool for current and future experimental treatments. In order to develop a quantitative marker to measure brain volume outcome, we analysed the longitudinal volumetric development of GM, white matter (WM) and lateral ventricles and correlated those with the clinical course. METHODS: One hundred twenty-two MRI scans of 35 patients (21 females; 14 males; age 15.3 ± 4.8 years) with genetically confirmed CLN3 disease were performed. A three-dimensional T1-weighted sequence was acquired with whole brain coverage. Volumetric segmentation of the brain was performed with the FreeSurfer image analysis suite. The clinical severity was assessed by the Hamburg jNCL score, a disease-specific scoring system. RESULTS: The volumes of supratentorial cortical GM and supratentorial WM, cerebellar GM, basal ganglia/thalamus and hippocampus significantly (r = - 0.86 to - 0.69, p < 0.0001) decreased with age, while the lateral ventricle volume increased (r = 0.68, p < 0.0001). Supratentorial WM volume correlated poorer with age (r = - 0.56, p = 0.0001). Supratentorial cortical GM volume showed the steepest (4.6% (± 0.2%)) and most uniform decrease with strongest correlation with age (r = - 0.86, p < 0.0001). In addition, a strong correlation with disease specific clinical scoring existed for the supratentorial cortical GM volume (r = 0.85, p = < 0.0001). CONCLUSION: Supratentorial cortical GM volume is a sensitive parameter for assessment of disease progression even in early and late disease stages and represents a potential reliable outcome measure for evaluation of experimental therapies.

Diffusion tensor imaging combined with T2 mapping to quantify changes in the skeletal muscle associated with training and endurance exercise in competitive triathletes.

OBJECTIVES: Diffusion tensor magnetic resonance imaging (DTI) and T2 mapping enable the detection of exercise-induced changes in the skeletal muscle microenvironment. This study prospectively quantified DTI metrics and T2 relaxation times of thigh muscles in competitive triathletes at rest and following a triathlon race in comparison with sedentary controls. METHODS: Twenty-two triathletes (males N = 16, females N = 6) and twenty-three controls (males N = 16, females N = 7) underwent magnetic resonance imaging (MRI) on a 3 T system at baseline (time point 1; 72 h at rest). Twelve triathletes (males N = 8, females N = 4) underwent a second scan (time point 2; 3 h of completing a triathlon race). The tensor eigenvalues (λ1, λ2, λ3), mean diffusivity (MD), fractional anisotropy (FA), and T2 times were compared between controls and triathletes at time point 1 and triathletes at time points 1 and 2 using independent and paired t tests. RESULTS: In comparison with the controls at time point 1, the T2 times of rectus femoris (RF, p < 0.02), adductor magnus (AM, p = 0.02), biceps femoris (BF, p < 0.001), semitendinosus (ST, p = 0.005), and semimembranosus (SM, p = 0.003) muscles were significantly increased in triathletes. At time point 2 in triathletes, the average tensor metrics (MD, λ3/ λ1) of BF, ST, and SM muscles increased (p < 0.05) and FA values in ST and SM muscles decreased (p < 0.03). T2 times were not significantly changed between both time points in triathletes. CONCLUSION: Our results indicate that this multiparametric MRI protocol allows detection and quantification of changes in the skeletal muscle microenvironment caused by endurance training and acute strenuous exercise. KEY POINTS: • Endurance training results in changes to the skeletal microstructure, which can be quantified using MRI-based diffusion tensor imaging. • The combined application of MRI diffusion tensor imaging and T2 mapping allows the differentiation of microstructural changes caused by active exercise or endurance training. • Environmental adaptations of the skeletal muscle caused by physical training are influenced by gender.

Prospective comparison of diffusion-weighted MRI and dynamic Gd-EOB-DTPA-enhanced MRI for detection and staging of hepatic fibrosis in primary sclerosing cholangitis.

PURPOSE: To assess the diagnostic value of multiparametric magnetic resonance imaging (MRI) including dynamic Gd-EOB-DTPA-enhanced (DCE) and diffusion-weighted (DW) imaging for diagnosis and staging of hepatic fibrosis in primary sclerosing cholangitis (PSC) using transient elastography as a standard reference. MATERIAL AND METHODS: Multiparametric MRI was prospectively performed on a 3.0-Tesla scanner in 47 patients (age 43.9±14.3 years). Transient elastography derived liver stiffness measurements (LSM), DCE-MRI derived parameters (hepatocellular uptake rate (Ki), arterial (Fa), portal venous (Fv) and total (Ft) blood flow, mean transit time (MTT), and extracellular volume (Ve)) and the apparent diffusion coefficient (ADC) were calculated. Correlation and univariate analysis of variance with post hoc pairwise comparison were applied to test for differences between LSM derived fibrosis stages (F0/F1, F2/3, F4). ROC curve analysis was used as a performance measure. RESULTS: Both ADC and Ki correlated significantly with LSM (r= -0.614; p<0.001 and r= -0.368; p=0.01). The ADC significantly discriminated fibrosis stages F0/1 from F2/3 and F4 (p<0.001). Discrimination of F0/1 from F2/3 and F4 reached a sensitivity/specificity of 0.917/0.821 and 0.8/0.929, respectively. Despite significant inter-subject effect for classification of fibrosis stages, post hoc pairwise comparison was not significant for Ki (p>0.096 for F0/1 from F2/3 and F4). LSM, ADC and Ki were significantly associated with serum-based liver functional tests, disease duration and spleen volume. CONCLUSION: DW-MRI provides a higher diagnostic performance for detection of hepatic fibrosis and cirrhosis in PSC patients in comparison to Gd-EOB-DTPA-enhanced DCE-MRI. KEY POINTS: • Both ADC and hepatocellular uptake rate (Ki) correlate significantly with liver stiffness (r= -0.614; p<0.001 and r= -0.368; p=0.01). • The DCE-imaging derived quantitative parameter hepatocellular uptake rate (Ki) fails to discriminate pairwise intergroup differences of hepatic fibrosis (p>0.09). • DWI is preferable to DCE-imaging for discrimination of fibrosis stages F0/1 to F2/3 (p<0.001) and F4 (p<0.001).

T1 Recovery Is Predominantly Found in Black Holes and Is Associated with Clinical Improvement in Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: Quantitative MR imaging parameters help to evaluate disease progression in multiple sclerosis and increase correlation with clinical disability. We therefore hypothesized that T1 values might be a marker for ongoing tissue damage or even remyelination and may help increase clinical correlation. MATERIALS AND METHODS: MR imaging was performed in 17 patients with relapsing-remitting MS at baseline and after 12 months of starting immunotherapy with dimethyl fumarate. On baseline images, lesion segmentation was performed for normal-appearing white matter, T2 hyperintense (FLAIR lesions), T1 hypointense (black holes), and contrast-enhancing lesions, and T1 relaxation times were obtained at baseline and after 12 months. Changes in clinical status were assessed by using the Expanded Disability Status Scale and Symbol Digit Modalities Test at both dates (Expanded Disability Status Scale-difference/Symbol Digit Modalities Test-diff). RESULTS: The highest T1 relaxation time at baseline was measured in black holes (1460.2 ± 209.46 ms) followed by FLAIR lesions (1400.38 ± 189.1 ms), pure FLAIR lesions (1327.5 ± 210.04 ms), contrast-enhancing lesions (1205.59 ± 199.95 ms), and normal-appearing white matter (851.34 ± 30.61 ms). After 12 months, T1 values had decreased significantly in black holes (1369.4 ± 267.81 ms), contrast-enhancing lesions (1079.57 ± 183.36 ms) (both P < .001), and normal-appearing white matter (841.98 ± 36.1 ms, P = .006). With the Jonckheere-Terpstra Test, better clinical scores were associated with decreasing T1 relaxation times in black holes (P < .05). CONCLUSIONS: T1 relaxation time is a useful quantitative MR imaging technique, which helps detect changes in MS lesions with time. We assume that these changes are associated with the degree of myelination within the lesions themselves and are pronounced in black holes. Additionally, decreasing T1 values in black holes were associated with clinical improvement.

Volumetric Description of Brain Atrophy in Neuronal Ceroid Lipofuscinosis 2: Supratentorial Gray Matter Shows Uniform Disease Progression.

BACKGROUND AND PURPOSE: Experimental therapies for ceroid lipofuscinosis, neuronal, 2 (CLN2), a genetic disorder of childhood associated with progressive brain atrophy, are currently being developed. Because quantitative descriptions of the natural course of brain volume loss are needed to evaluate novel therapies, we performed MR imaging volumetry of patients with CLN2 to identify a suitable MR imaging marker of disease progression. MATERIALS AND METHODS: Thirteen patients (8 females, 5 males) were recruited from a prospective natural disease cohort of patients with neuronal ceroid lipofuscinosis. Repeated MR imaging volumetric analysis (29 datasets) was performed by using the FreeSurfer Software Suite. Follow-up time ranged from 8 months to 5.3 years. MR imaging-segmented brain volumes were correlated to patient age and clinical scores. RESULTS: Segmented brain volumes correlated significantly with patient age (lateral ventricles, r = 0.606, P = .001; supratentorial cortical GM, r = -0.913, P < .001; supratentorial WM, r = -0.865, P < .001; basal ganglia/thalamus, r = -0.832, P < .001; cerebellar GM, r = -0.659, P < .001; cerebellar WM, r = -0.830, P < .001) and clinical scores (lateral ventricles, r = -0.692, P < .001; supratentorial cortical GM, r = 0.862, P < .001; supratentorial WM, r = 0.735, P < .001; basal ganglia/thalamus, r = 0.758, P < .001; cerebellar GM, r = 0.609, P = .001; cerebellar WM, r = 0.638, P < .001). Notably, supratentorial cortical GM showed a uniform decline across the patient cohort. During late stages of the disease when the clinical score was zero, segmented brain volumes still correlated with patient age; this finding suggests that MR imaging volumetry allows quantitative assessment of disease progression at stages when it cannot be detected by clinical assessment alone. CONCLUSIONS: Automated MR imaging volumetry, as a nonsubjective and highly sensitive tool, is feasible in CLN2 disease and provides a quantitative basis to evaluate novel experimental therapies.

Chronic T2 Lesions in Multiple Sclerosis are Heterogeneous Regarding Phase MR Imaging.

PURPOSE: Phase imaging provides additional information on multiple sclerosis (MS) lesions and may in combination with mean diffusivity (MD) and magnetization transfer ratio (MTR) help differentiating heterogeneity of MS lesion pathology. METHODS: Magnetic resonance imaging (MRI) was performed in 23 MS patients including diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), and SWI. Mean values (MTR, MD, and homodyne filtered phase) from 138 chronic MS lesions and normal appearing white matter (NAWM) were obtained and correlations examined. For explorative analysis, a divisive hierarchical clustering algorithm was applied. RESULTS: Phase characteristics were an independent characteristic of chronic T2 lesions, as MTR and MD were not correlated with phase values (R = - 0.23, R = - 0.18). Dependent on MTR, MD, and phase, cluster analysis led to five lesion groups. Of the two groups with phase values close to NAWM, one presented with highest MD and most severe MTR decrease (p = 0.01), the other with slight MD increase and MTR decrease. Two lesion groups with highest phase values (p = 0.01) displayed slightly increased MD and moderate decrease in MTR. Clinical data including EDSS, disease duration, and age did not differ significantly between groups. CONCLUSIONS: Increased phase is predominantly detectable in lesions with clear MTR decrease but only moderate MD increase. Phase images seem to represent an independent parameter for MS lesion characterization and may provide additional information on MS lesion heterogeneity.

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.

Reversible, irreversible and effective transverse relaxation rates in normal aging brain at 3T.

Quantitative transverse relaxation rates in normal aging brain are essential to investigate pathologies associated with iron accumulation and tissue degeneration. Since absolute values depend on imaging methods and magnetic field strengths, continuous evaluation of specific reference values remains requisite. Multi-echo turbo spin echo and multi-echo gradient recalled echo imaging sequences were applied to 66 healthy subjects (18-84years) at 3T to quantify the irreversible (R2), effective (R2*) and reversible (R2'=R2*-R2) transverse relaxation rates. Representative regions-of-interest (ROIs) were determined automatically in gray matter (GM) and white matter (WM) on T1-weighted scans. Phantom experiments of different sized iron-oxide particles were conducted to explore the correlation of R2' related to R2 for the evaluation of the size of iron deposits. R2 decreased with age for the majority of ROIs, but increased for putamen, head of caudate nucleus and nucleus accumbens. R2* and R2' increased with age in deep GM structures except for the thalamus. R2* and R2' showed a distinct dependency on fiber orientation in exemplary WM regions. R2', R2 and R2* were strongly linear proportional to age-related iron content in deep GM with slopes of 0.88, 0.18 and 1.08 in [1/s/mg Fe per 100g wet tissue] and intercepts of 1.69, 9.25 and 10.69 in [1/s], respectively. Linear and non-linear curve fitting of R2' vs. R2 in phantoms revealed increased slopes with increasing particle size. In vivo, averaged R2' vs. R2 data points of patients with Parkinson's disease and progressive supranuclear palsy were above the fitted curves of healthy subjects suggesting larger sized iron deposits in these neurodegenerative diseases. Decreased R2 with age may reflect physiological tissue degeneration, whereas increased R2* and R2' with age most likely denote physiological iron accumulation. The low intercept of R2' vs. iron content suggests a nearly sole sensitivity of R2' to iron in deep GM, potentially allowing a more specific estimation of the iron content than R2 or R2*. Since R2* and R2' depend on the fiber orientation, their feasibility to estimate iron content in WM is challenging. The analysis of R2' related to R2 may provide valuable information about the size of iron deposits.

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.

MR imaging assessment of tumor perfusion and 3D segmented volume at baseline, during treatment, and at tumor progression in children with newly diagnosed diffuse intrinsic pontine glioma.

BACKGROUND AND PURPOSE: DIPG is among the most devastating brain tumors in children, necessitating the development of novel treatment strategies and advanced imaging markers such as perfusion to adequately monitor clinical trials. This study investigated tumor perfusion and 3D segmented tumor volume as predictive markers for outcome in children with newly diagnosed DIPG. METHODS: Imaging data were assessed at baseline, during, and after RT, and every other month thereafter until tumor progression for 35 patients (ages 2-16 years) with newly diagnosed DIPG enrolled in the phase I clinical study, NCT00472017. Patients were treated with conformal RT and vandetanib, a vascular endothelial growth factor receptor 2 inhibitor. RESULTS: Tumor perfusion increased and tumor volume decreased during combined RT and vandetanib therapy. These changes slowly diminished in follow-up scans until tumor progression. However, increased tumor perfusion and decreased tumor volume during combined therapy were associated with longer PFS. Apart from a longer OS for patients who showed elevated tumor perfusion after RT, there was no association for tumor volume and other perfusion variables with OS. CONCLUSIONS: Our results suggest that tumor perfusion may be a useful predictive marker for the assessment of treatment response and tumor progression in children with DIPG treated with both RT and vandetanib. The assessment of tumor perfusion yields valuable information about tumor microvascular status and its response to therapy, which may help better understand the biology of DIPGs and monitor novel treatment strategies in future 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.

Quantitative diffusion-weighted and dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging analysis of T2 hypointense lesion components in pediatric diffuse intrinsic pontine glioma.

BACKGROUND AND PURPOSE: Focal anaplasia characterized by T2 hypointensity, signal-intensity enhancement on postcontrast T1-weighted MR imaging and restricted water diffusion has been reported in a patient with juvenile pilocytic astrocytoma. We identified T2(HOF) with these MR imaging characteristics in children with DIPG and hypothesized that these represent areas of focal anaplasia; and may, therefore, have increased perfusion properties and should be characterized by increased perfusion. Thus, we used DSC to investigate our hypothesis. MATERIALS AND METHODS: We retrospectively reviewed the baseline MR imaging scans of 86 patients (49 girls, 37 boys; median age, 6.1 years; range, 1.1-17.6 years) treated for DIPG at our hospital (2004-2009). T2(HOF) with the described MR imaging characteristics was identified in 10 patients. We used a region of interest-based approach to compare the ADC, FA, rCBV, rCBF, and rMTT of T2(HOF) with those of the typical T2(HRT). RESULTS: The ADC of T2(HOF) with the specified MR imaging characteristics was significantly lower than that of T2(HRT) (range, 0.71-1.95 µm(2)/ms versus 1.36-2.13 µm(2)/ms; P < .01); and the FA (range, 0.12-0.34 versus 0.07-0.24; P = .03) and rCBV (range, 0.4-2.62 versus 0.23-1.57; P = .01) values of T2(HOF)s were significantly higher. CONCLUSIONS: Our data suggest that T2(HOF) in DIPG may represent areas of focal anaplasia and underline the importance of regional, rather than global, tumor-field analysis. T2(HOF) may be the ideal target when stereotactic biopsy of tumors that present with an inhomogeneous T2 signal intensity is considered.

Attenuation of cerebral venous contrast in susceptibility-weighted imaging of spontaneously breathing pediatric patients sedated with propofol.

BACKGROUND AND PURPOSE: SWI is known for its detailed visualization of the cerebral venous system and seems to be a promising tool for early detection of cerebrovascular pathologies in children, who are frequently sedated for MR imaging. Because sedation influences cerebral hemodynamics, we hypothesized that it would affect cerebral venous contrast in SWI. MATERIALS AND METHODS: SWI (125 examinations) of 26 patients (age, 2-16 years) was reviewed in this study. Images were acquired of patients sedated with propofol. Reviewers classified the images by weak or strong venous contrast. Physiologic data, such as etCO(2), BP, age, and CBF by arterial spin-labeling, were monitored and collected during MR imaging. A generalized estimating equation approach was used to model associations of these parameters with venous contrast. RESULTS: EtCO(2) and CBF were found to correlate with venous contrast, suggesting that patients with high etCO(2) and CBF have weak contrast and patients with low etCO(2) and CBF have strong contrast. BP was also found to correlate with the venous contrast of SWI, suggesting that patients with high BP have strong venous contrast. No significant correlations were found for any other physiologic parameters. CONCLUSIONS: We found that the venous contrast in SWI is affected by propofol sedation in spontaneously breathing patients. We also found that low etCO(2), low CBF, and high BP are associated with strong venous contrast. Reviewing SWI data in light of physiologic measures may therefore help prevent potential misinterpretations of weak venous contrast in SWI examinations under propofol sedation.

High resolution susceptibility weighted MR-imaging of brain tumors during the application of a gaseous agent.

PURPOSE: To employ a high resolution blood oxygenation level dependent (BOLD) method called susceptibility weighted imaging (SWI) together with the breathing of carbogen to investigate the response of cerebral tumors to this breathing gas and to assess tumor anatomy at high resolution. METHODS: Five patients with cerebral tumors (four glioblastoma multiforme, one astrocytoma [WHO grade II]) were studied using a susceptibility weighted 3D gradient echo, first order velocity compensated sequence (TE = 45 ms, TR = 67 ms, alpha = 25 degrees , FOV = 256 x 192 x 64 mm(3), typical matrix = 512 x 192 x 64), on a 1.5 T MR scanner while they were breathing air and carbogen. Signal changes between the two breathing conditions were investigated. RESULTS: The glioblastomas showed strong but heterogeneous signal changes between carbogen and air breathing, with changes between + 22.4 +/- 4.9 % at the perimeter of the tumors and - 5.0 +/- 0.4 % in peritumoral areas that appeared hyperintense on T (2)-weighted images. The astrocytoma displayed a signal decrease during carbogen breathing (- 4.1 +/- 0.1 % to - 6.8 +/- 0.3 % in peritumoral areas that correspond to hyperintense regions on T (2)-weighted images, and - 3.1 +/- 0.1 % in the tumor-center). CONCLUSIONS: SWI provides high resolution images of cerebral anatomy and venous vascularization. Combined with hypercapnia it allows for regional assessment of tumor activity.