Robustness of radiomics to variations in segmentation methods in multimodal brain MRI.

Radiomics in neuroimaging uses fully automatic segmentation to delineate the anatomical areas for which radiomic features are computed. However, differences among these segmentation methods affect radiomic features to an unknown extent. A scan-rescan dataset (n = 46) of T1-weighted and diffusion tensor images was used. Subjects were split into a sleep-deprivation and a control group. Scans were segmented using four segmentation methods from which radiomic features were computed. First, we measured segmentation agreement using the Dice-coefficient. Second, robustness and reproducibility of radiomic features were measured using the intraclass correlation coefficient (ICC). Last, difference in predictive power was assessed using the Friedman-test on performance in a radiomics-based sleep deprivation classification application. Segmentation agreement was generally high (interquartile range = 0.77-0.90) and median feature robustness to segmentation method variation was higher (ICC > 0.7) than scan-rescan reproducibility (ICC 0.3-0.8). However, classification performance differed significantly among segmentation methods (p < 0.001) ranging from 77 to 84%. Accuracy was higher for more recent deep learning-based segmentation methods. Despite high agreement among segmentation methods, subtle differences significantly affected radiomic features and their predictive power. Consequently, the effect of differences in segmentation methods should be taken into account when designing and evaluating radiomics-based research methods.

Vessel Type Determined by Vessel Architectural Imaging Improves Differentiation between Early Tumor Progression and Pseudoprogression in Glioblastoma.

BACKGROUND AND PURPOSE: Currently available perfusion parameters are limited in differentiating early tumor progression and pseudoprogression with no insight about vessel size and type. We aimed to investigate differences in vessel size and type between early tumor progression and pseudoprogression in posttreatment glioblastoma and to demonstrate diagnostic performance using vessel architectural imaging. MATERIALS AND METHODS: Fifty-eight patients with enlarging contrast-enhancing masses in posttreatment glioblastomas underwent simultaneous gradient recalled-echo and spin-echo dynamic susceptibility contrast imaging. Relative CBV and vessel architectural imaging parameters, including the relative vessel size index, peak shift between gradient recalled echo and spin-echo bolus signal peaks, and arterial dominance scores using spatial dominance of arterial/venous vessel type, were calculated and compared between the 2 conditions. The area under the curve and cross-validation were performed to compare the diagnostic performance of the relative CBV, vessel architectural imaging parameters, and their combinations. RESULTS: There were 41 patients with early tumor progression and 17 patients with pseudoprogression. Relative to pseudoprogression, early tumor progression showed a lower peak shift (-0.02 versus 0.33, P = .02) and a lower arterial dominance score (1.46 versus 2.11, P = .001), indicating venous dominance. Patients with early tumor progression had higher relative CBV (1.88 versus 1.38, P = .02) and a tendency toward a larger relative vessel size index (99.67 versus 83.17, P = .15) than those with pseudoprogression. Combining arterial dominance scores and relative CBV showed significantly higher diagnostic performance (area under the curve = 0.82; 95% CI, 0.70-0.94; P = .02) than relative CBV alone (area under the curve = 0.64; 95% CI, 0.49-0.79) in distinguishing early tumor progression from pseudoprogression. CONCLUSIONS: Vessel architectural imaging significantly improved the diagnostic performance of relative CBV by demonstrating venous dominance and a tendency toward larger vessel size in early tumor progression.

Methylphenidate Effects on Cortical Thickness in Children and Adults with Attention-Deficit/Hyperactivity Disorder: A Randomized Clinical Trial.

BACKGROUND AND PURPOSE: Although methylphenidate is frequently used to treat children with attention-deficit/hyperactivity disorder, it is currently unknown how methylphenidate affects brain development. In a randomized controlled trial, we investigated whether the cortical effects of methylphenidate are modulated by age. MATERIALS AND METHODS: Between June 1, 2011, and June 15, 2015, we conducted a randomized, double-blind, placebo-controlled trial (Effects of Psychotropic Drugs on Developing Brain-Methylphenidate) in 99 males with attention-deficit/hyperactivity disorder (according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria) from referral centers in the greater Amsterdam area in the Netherlands. The trial was registered on March 24, 2011 (identifier NL34509.000.10) and subsequently at the Netherlands National Trial Register (identifier NTR3103). Participants (first enrolled October 13, 2011) were 10-12 years or 23-40 years of age and randomized to treatment with either methylphenidate or a placebo for 16 weeks. Our main outcome was a change in cortical thickness in predefined ROIs as measured by MR imaging pre- and posttreatment. RESULTS: We observed a time × medication × age interaction (F[1,88.825] = 4.316, P < .05) for the right medial cortex ROI, where methylphenidate treatment yielded less cortical thinning in children, but not in adults or the placebo groups. CONCLUSIONS: Our finding that the effects of methylphenidate on right medial cortical thickness differ between children and adults infers that the drug affects gray matter development in this brain region. This warrants replication in larger groups with longer follow-up to determine whether this effect can also be observed in other cortical brain regions and whether it may have long-term consequences.

Clinical Value of Vascular Permeability Estimates Using Dynamic Susceptibility Contrast MRI: Improved Diagnostic Performance in Distinguishing Hypervascular Primary CNS Lymphoma from Glioblastoma.

BACKGROUND AND PURPOSE: A small subset of primary central nervous system lymphomas exhibits high cerebral blood volume, which is indistinguishable from that in glioblastoma on dynamic susceptibility contrast MR imaging. Our study aimed to test whether estimates of combined perfusion and vascular permeability metrics derived from DSC-MR imaging can improve the diagnostic performance in differentiating hypervascular primary central nervous system lymphoma from glioblastoma. MATERIALS AND METHODS: A total of 119 patients (with 30 primary central nervous system lymphomas and 89 glioblastomas) exhibited hypervascular foci using the reference method of leakage-corrected CBV (reference-normalized CBV). An alternative postprocessing method used the tissue residue function to calculate vascular permeability (extraction fraction), leakage-corrected CBV, cerebral blood flow, and mean transit time. Parameters were compared using Mann-Whitney U tests, and the diagnostic performance to distinguish primary central nervous system lymphoma from glioblastoma was calculated using the area under the curve from the receiver operating characteristic curve and was cross-validated with bootstrapping. RESULTS: Hypervascular primary central nervous system lymphoma showed similar leakage-corrected normalized CBV and leakage-corrected CBV compared with glioblastoma (P > .05); however, primary central nervous system lymphoma exhibited a significantly higher extraction fraction (P < .001) and CBF (P = .01) and shorter MTT (P < .001) than glioblastoma. The extraction fraction showed the highest diagnostic performance (the area under the receiver operating characteristic curve [AUC], 0.78; 95% confidence interval, 0.69-0.85) for distinguishing hypervascular primary central nervous system lymphoma from glioblastoma, with a significantly higher performance than both CBV (AUC, 0.53-0.59, largest P = .02) and CBF (AUC, 0.72) and MTT (AUC, 0.71). CONCLUSIONS: Estimation of vascular permeability with DSC-MR imaging further characterizes hypervascular primary central nervous system lymphoma and improves diagnostic performance in glioblastoma differentiation.

Improved Automatic Segmentation of White Matter Hyperintensities in MRI Based on Multilevel Lesion Features.

Brain white matter hyperintensities (WMHs) are linked to increased risk of cerebrovascular and neurodegenerative diseases among the elderly. Consequently, detection and characterization of WMHs are of significant clinical importance. We propose a novel approach for WMH segmentation from multi-contrast MRI where both voxel-based and lesion-based information are used to improve overall performance in both volume-oriented and object-oriented metrics. Our segmentation method (AMOS-2D) consists of four stages following a "generate-and-test" approach: pre-processing, Gaussian white matter (WM) modelling, hierarchical multi-threshold WMH segmentation and object-based WMH filtering using support vector machines. Data from 28 subjects was used in this study covering a wide range of lesion loads. Volumetric T1-weighted images and 2D fluid attenuated inversion recovery (FLAIR) images were used as basis for the WM model and lesion masks defined manually in each subject by experts were used for training and evaluating the proposed method. The method obtained an average agreement (in terms of the Dice similarity coefficient, DSC) with experts equivalent to inter-expert agreement both in terms of WMH number (DSC = 0.637 vs. 0.651) and volume (DSC = 0.743 vs. 0.781). It allowed higher accuracy in detecting WMH compared to alternative methods tested and was further found to be insensitive to WMH lesion burden. Good agreement with expert annotations combined with stable performance largely independent of lesion burden suggests that AMOS-2D will be a valuable tool for fully automated WMH segmentation in patients with cerebrovascular and neurodegenerative pathologies.

Neurobiological correlates of depressive symptoms in people with subjective and mild cognitive impairment.

OBJECTIVE: To test the hypothesis that depressive symptoms correlate with Alzheimer's disease (AD) type changes in CSF and structural and functional imaging including hippocampus volume, cortical thickness, white matter lesions, Diffusion tensor imaging (DTI), and fluoro-deoxy-glucose positron emission tomography (FDG-PET) in patient with subjective (SCI) and mild (MCI) cognitive impairment. METHOD: In 60 patients, depressive symptoms were assessed using the Geriatric Depression Scale. The subjects underwent MRI, 18F-FDG PET imaging, and lumbar CSF extraction. RESULTS: Subjects with depressive symptoms (n=24) did not have more pathological AD biomarkers than non-depressed. Uncorrected there were trends towards larger hippocampal volumes (P=0.06), less orbital WM damage measured by DTI (P=0.10), and higher orbital glucose metabolism (P=0.02) in the depressed group. The findings were similar when SCI and MCI were analyzed separately. Similarly, in patients with pathological CSF biomarkers (i.e., predementia AD, n=24), we found that correlations between scores on GDS and CSF Aß42 and P-tau indicated less severe AD-specific CSF changes with increasing depression. CONCLUSION: Depressive symptoms are common in SCI/MCI, but are not associated with pathological imaging or CSF biomarkers of AD. Depression can explain cognitive impairment in SCI/MCI or add to cognitive impairment leading to an earlier clinical investigation in predementia AD.

White matter characteristics and cognition in prenatally opiate- and polysubstance-exposed children: a diffusion tensor imaging study.

BACKGROUND AND PURPOSE: Prenatal drug exposure may influence the developing brain. Our aim was to study WM characteristics with DTI in children with prenatal opiate and polysubstance exposure and in controls. We assessed whether group differences in FA, DA, and DR could be found and related to cognitive function. MATERIALS AND METHODS: The study was approved by a committee for medical research ethics. Parents signed an informed consent; children gave spoken consent. Our sample included 14 prenatally substance-exposed adopted children (5 girls; age range, 8.6-13.9 years; mean, 11.3 +/- 1.7 years) and 14 control children (7 girls; age range, 9.0-10.2 years; mean, 9.8 +/- 0.3 years). Tract-based spatial statistics were used to define a common WM skeleton for the sample, and FA was compared between groups throughout the skeleton, controlling for age and sex. Clusters of significant group differences >or=100 voxels (P <. 05) were identified. FA, DA, and DR within clusters were correlated with cognitive function. RESULTS: Ten clusters of FA group differences, mostly in central, posterior, and inferior parts of the brain, were identified (P <. 05), showing lower FA in substance-exposed children. FA and DA correlated positively and DR, negatively with cognitive function across groups. CONCLUSIONS: Prenatally substance-exposed children exhibited lower FA in restricted areas of WM, mostly relatively central, inferior, and posterior, where myelination occurs early in development. Myelin in these areas may be particularly vulnerable to prenatal substance exposure. FA and DR related moderately to cognitive function. Potential confounding factors existed and were considered.

An automatic procedure for normalization of cerebral blood volume maps in dynamic susceptibility contrast-based glioma imaging.

To characterize gliomas from dynamic susceptibility contrast (DSC)-based cerebral blood volume (CBV) maps, a CBV value from a normal-appearing region of interest is typically identified manually and used to normalize the CBV maps. This method is user-dependent and time-consuming. We propose an alternative approach based on automatic identification of normal-appearing first-pass curves from brain tissue. Our results in 101 patients suggest similar or better diagnostic accuracy values than the manual approach.

Venous saturation slab causes overestimation of stenosis length in two-dimensional time-of-flight magnetic resonance angiography.

BACKGROUND: The use of downstream saturation slabs in two-dimensional time-of-flight magnetic resonance angiography (2D TOF MRA) of the arterial system eliminates signal from regions with countercurrent flow, as seen in veins, but possibly also beyond arterial stenoses because of flow turbulence. PURPOSE: To investigate the contribution of a downstream saturation slab to signal intensity (SI) loss beyond stenoses at 2D TOF MRA. MATERIAL AND METHODS: 2D TOF MRA was performed on a bifurcation phantom with a tight stenosis at 1.5T during pulsatile flow. Qualitative and quantitative evaluations of stenosis delineation were performed with different echo times (TE) (3.7 or 7.0 ms), spatial resolution (1 x 1 x 1 or 1 x 1 x 5 mm(3)), and with or without a downstream saturation slab. For reference, a high-resolution contrast-enhanced sequence without flow was obtained. RESULTS: The downstream saturation slab caused severe signal loss immediately distal to the stenosis, causing overestimation of stenosis length. This region corresponded with a region of poststenotic flow jet, where turbulence is expected. With increase in TE, there was some increased SI loss at the level of maximum stenosis. A lower spatial resolution resulted in overall poorer delineation of the stenosis. CONCLUSION: Using clinically relevant sequence parameters, the use of a downstream saturation slab at 2D TOF MRA was found to be a major contributor to signal loss in stenotic regions, which can result in an overestimation of stenosis length.

Multimodal imaging in mild cognitive impairment: Metabolism, morphometry and diffusion of the temporal-parietal memory network.

This study compared sensitivity of FDG-PET, MR morphometry, and diffusion tensor imaging (DTI) derived fractional anisotropy (FA) measures to diagnosis and memory function in mild cognitive impairment (MCI). Patients (n=44) and normal controls (NC, n=22) underwent FDG-PET and MRI scanning yielding measures of metabolism, morphometry and FA in nine temporal and parietal areas affected by Alzheimer's disease and involved in the episodic memory network. Patients also underwent memory testing (RAVLT). Logistic regression analysis yielded 100% diagnostic accuracy when all methods and ROIs were combined, but none of the variables then served as unique predictors. Within separate ROIs, diagnostic accuracy for the methods combined ranged from 65.6% (parahippocampal gyrus) to 73.4 (inferior parietal cortex). Morphometry predicted diagnostic group for most ROIs. PET and FA did not uniquely predict group, but a trend was seen for the precuneus metabolism. For the MCI group, stepwise regression analyses predicting memory scores were performed with the same methods and ROIs. Hippocampal volume and FA of the retrosplenial WM predicted learning, and hippocampal metabolism and parahippocampal cortical thickness predicted 5 minute recall. No variable predicted 30 minute recall independently of learning. In conclusion, higher diagnostic accuracy was achieved when multiple methods and ROIs were combined, but morphometry showed superior diagnostic sensitivity. Metabolism, morphometry and FA all uniquely explained memory performance, making a multi-modal approach superior. Memory variation in MCI is likely related to conversion risk, and the results indicate potential for improved predictive power by the use of multimodal imaging.

A piglet model for detection of hypoxic-ischemic brain injury with magnetic resonance imaging.

BACKGROUND: Early detection of hypoxic-ischemic (HI) injury in the asphyxic newborn is important because present prognostic factors are inadequate. Furthermore, therapeutic interventions may have additional benefit if initiated in time. PURPOSE: To assess whether the use of a combined protocol including conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), and proton MR spectroscopy (MRS) could detect pathological findings in a piglet model 7 hours after HI. MATERIAL AND METHODS: Ten piglets were submitted to HI for 30 min followed by reoxygenation with 21% O2 for 7 hours. MRI at 1.5T was done prior to and 7 hours after the HI. Single-voxel proton MRS was performed, and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in the basal ganglia. MRS identified N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate (Lac). Histology and microtubule-associated protein 2 (MAP-2) staining was performed in the basal ganglia at the end of the experiment. RESULTS: Compared to baseline, ADC, NAA/Cho, and NAA/Cr were significantly reduced after 7 hours (P<0.001, P=0.01, and P=0.05, respectively) and FA values were increased (P<0.025). The ratios of Lac/Cho and Lac/NAA were significantly higher after 7 hours compared to baseline (P<0.001). Presence of necrosis correlated well with reduced ADC (R(S)=0.91) and presence of Lac (R(S)=0.80). Histology and MAP-2 staining showed more than 90% necrosis in eight piglets, 60% in one piglet, and no necrosis in one piglet. CONCLUSION: Diffusion MRI and proton MRS can detect HI injury in the piglet brain 7 hours after hypoxia. DWI and MRS can be used to give useful prognostic information. This piglet model may potentially be used to mimic clinical situations and is suitable for further research investigating HI injury.

Quantitative renal cortical perfusion in human subjects with magnetic resonance imaging using iron-oxide nanoparticles: influence of T1 shortening.

BACKGROUND: Using conventional contrast agents, the technique of quantitative perfusion by observing the transport of a bolus with magnetic resonance imaging (MRI) is limited to the brain due to extravascular leakage. PURPOSE: To perform quantitative perfusion measurements in humans with an intravascular contrast agent, and to estimate the influence of the T1 relaxivity of the contrast agent on the first-pass response. MATERIAL AND METHODS: Renal cortical perfusion was measured quantitatively in six patients with unilateral renal artery stenosis using a rapid gradient double-echo sequence in combination with an intravenous bolus injection of NC100150 Injection, an intravascular contrast agent based on iron-oxide nanoparticles. The influence of T1 relaxivity was measured by comparing perfusion results based on single- and double-echo data. RESULTS: The mean values of cortical blood flow, cortical blood volume, and mean transit time in the normal kidneys were measured to 339+/-60 ml/min/100 g, 41+/-8 ml/100 g, and 7.3+/-1.0 s, respectively, based on double-echo data. The corresponding results based on single-echo data, which are not compensated for the T1 relaxivity, were 254+/-47 ml/min/100 g, 27+/-3 ml/100 g, and 6+/-1.2 s, respectively. CONCLUSION: The use of a double-echo sequence enabled elimination of confounding T1 effects and consequent systematic underestimation of the perfusion.

Morphometric changes in the episodic memory network and tau pathologic features correlate with memory performance in patients with mild cognitive impairment.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) may affect several cognitive domains, including attention and reasoning, but is often first characterized by memory deficits. The purpose of this study was to ask these 2 questions: 1) Can levels of CSF tau proteins and amyloid beta 42 peptide explain thinning of the cerebral cortex in patients with MCI? 2) How are brain morphometry, CSF biomarkers, and apolipoprotein E (APOE) allelic variation related to episodic memory function in MCI? MATERIALS AND METHODS: Hippocampal volume and cortical thickness were estimated by MR imaging and compared for patients with MCI (n = 18) and healthy controls (n = 18). In addition, regions of interest (ROIs) were selected in areas where the MCI group had atrophy and which overlapped with the episodic memory network (temporal, entorhinal, inferior parietal, precuneus/posterior cingulate, and frontal). Relationships among morphometry, CSF biomarkers, APOE, and memory were tested. The analyses were repeated with an independent sample of patients with MCI (n = 19). RESULTS: Patients with MCI and pathologic CSF values had hippocampal atrophy. However, both patients with pathologic and patients with nonpathologic CSF had a thinner cortex outside the hippocampal area. CSF pathology was related to hippocampal volume, whereas relationships with cortical thickness were found mainly in one of the samples. Morphometry correlated robustly with memory performance across MCI samples, whereas less stable results were found for tau protein. CONCLUSION: The differences in hippocampal volume between the MCI and the healthy control groups were only found in patients with pathologic CSF biomarkers, whereas differences in cortical thickness were also found for patients without such pathologic features. Morphometry in areas in the episodic memory network was robustly correlated with memory performance. It is speculated that atrophy in these areas may be associated with the memory problems seen in MCI.

Histogram analysis of MR imaging-derived cerebral blood volume maps: combined glioma grading and identification of low-grade oligodendroglial subtypes.

BACKGROUND AND PURPOSE: Inclusion of oligodendroglial tumors may confound the utility of MR based glioma grading. Our aim was, first, to assess retrospectively whether a histogram-analysis method of MR perfusion images may both grade gliomas and differentiate between low-grade oligodendroglial tumors with or without loss of heterozygosity (LOH) on 1p/19q and, second, to assess retrospectively whether low-grade oligodendroglial subtypes can be identified in a population of patients with high-grade and low-grade astrocytic and oligodendroglial tumors. MATERIALS AND METHODS: Fifty-two patients (23 women, 29 men; mean age, 52 years; range, 19-78 years) with histologically confirmed gliomas were imaged by using dynamic susceptibility contrast MR imaging at 1.5T. Relative cerebral blood volume (rCBV) maps were created, and 4 neuroradiologists defined the glioma volumes independently. Averaged over the 4 observers, a histogram-analysis method was used to assess the normalized histogram peak height of the glioma rCBV distributions. RESULTS: Of the 52 patients, 22 had oligodendroglial tumors. The histogram method was able to differentiate high-grade gliomas (HGGs) from low-grade gliomas (LGGs) (Mann-Whitney U test, P < .001) and to identify low-grade oligodendroglial subtypes (P = .009). The corresponding intraclass correlation coefficients were 0.902 and 0.801, respectively. The sensitivity and specificity in terms of differentiating low-grade oligodendroglial tumors without LOH on 1p/19q from the other tumors was 100% (6/6) and 91% (42/46), respectively. CONCLUSION: With histology as a reference, our results suggest that histogram analysis of MR imaging-derived rCBV maps can differentiate HGGs from LGGs as well as low-grade oligodendroglial subtypes with high interobserver agreement. Also, the method was able to identify low-grade oligodendroglial tumors without LOH on 1p/19q in a population of patients with astrocytic and oligodendroglial tumors.

Volumetric cerebral characteristics of children exposed to opiates and other substances in utero.

Morphometric cerebral characteristics were studied in children with prenatal poly-substance exposure (n=14) compared to controls (n=14) without such exposure. Ten of the substance-exposed children were born to mothers who used opiates (heroin) throughout the pregnancy. Groups were compared across 16 brain measures: cortical gray matter, cerebral white matter, hippocampus, amygdala, thalamus, accumbens area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, lateral ventricles, inferior lateral ventricles, and the 3rd and 4th ventricles. In addition, continuous measurement of thickness across the entire cortical mantle was performed. Volumetric characteristics were correlated with ability and questionnaire assessments 2 years prior to scan. Compared to controls, the substance-exposed children had smaller intracranial and brain volumes, including smaller cerebral cortex, amygdala, accumbens area, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, and inferior lateral ventricles, and thinner cortex of the right anterior cingulate and lateral orbitofrontal cortex. Pallidum and putamen appeared especially reduced in the subgroup exposed to opiates. Only volumes of the right anterior cingulate, the right lateral orbitofrontal cortex and the accumbens area, showed some association with ability and questionnaire measures. The sample studied is rare and hence small, so conclusions cannot be drawn with certainty. Morphometric group differences were observed, but associations with previous behavioral assessment were generally weak. Some of the volumetric differences, particularly thinner cortex in part of the right lateral orbitofrontal cortex, may be moderately involved in cognitive and behavioral difficulties more frequently experienced by opiate and poly-substance-exposed children.

Diaschisis after thalamic stroke: a comparison of metabolic and structural changes in a patient with amnesic syndrome.

INTRODUCTION: We present a patient with a left anteromedial thalamic lesion with an amnesic syndrome. The patient underwent neuropsychological testing, cerebrospinal fluid (CSF) analyses, magnetic resonance imaging (MRI) [T2, flair, and diffusion tensor imaging (DTI)] and [18F]-2-fluoro-deoxy-d-glucose positron emission tomography (FDG-PET) to assess indirect effects of thalamic lesions on cortical function. CASE REPORT: A 67-year-old right-handed woman was admitted to a university-based memory unit because of memory and concentration problems. Neuropsychological testing revealed dysfunction of episodic memory, semantic memory and working memory. General intellectual function and attention capacity were preserved. MRI revealed an anteromedial thalamic lesion in the left hemisphere. FDG-PET showed decreased uptake in the frontal, parietal and temporal lobes of the left hemisphere. Regions of interest (ROI) in white matter were selected and left and right hemispheres were compared. Fractional anisotropy (FA) in ROI representing thalamo-cortical connections were decreased in the left hemisphere when compared with the right. CONCLUSION: The results show the importance of a network that include the anterior and dorsomedian nuclei, which influence the activity in areas of the cortex responsible for memory processes. The imaging findings suggest that areas of cortical diaschisis after thalamic infarction correspond to areas affected by thalamo-cortical fibre loss as measured with FA.

Contrast-enhanced dynamic magnetic resonance imaging of finger joints in osteoarthritis and rheumatoid arthritis: an analysis based on pharmacokinetic modeling.

PURPOSE: To investigate a two-compartment kinetic model applied to the dynamic time course of contrast enhancement as a method to differentiate between finger-joint synovitis in established osteoarthritis (OA) and rheumatoid arthritis (RA). MATERIAL AND METHODS: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of one hand in 19 patients and six healthy volunteers was undertaken. Eight patients had OA of the hand and eleven patients had RA. From the signal intensity curves, the three parameters Kps (endothelial transfer constant), Kep (elimination rate constant from extracellular space back to plasma) and Kel (elimination rate constant from plasma by renal excretion) were calculated. RESULTS: The rate constant Kps showed the best separation between the groups with significantly higher values in the RA group compared to the OA group (P<0.005) and in the OA group compared to the control group (P<0.005). Significantly higher values of Kep were also found in the RA group compared with the OA group (P<0.005). CONCLUSION: DCE-MRI may provide useful information that can help differentiate synovitis in OA from synovitis in RA.

New intravascular contrast agent applied to dynamic contrast enhanced MR imaging of human breast cancer.

PURPOSE: To evaluate the feasibility of using dynamic contrast-enhanced MR imaging with a new intravascular contrast agent in grading human breast cancer. MATERIAL AND METHODS: 23 patients with 27 breast tumors (21 carcinomas and 6 fibroadenomas) were examined with dynamic MR imaging after administration of Clariscan, an iron oxide nanoparticle with large T1 relaxivity and a long plasma half life. A 3D T1-weighted gradient echo sequence with an acquisition time of 60 s was repeated at regular intervals of 3-5 min before and up to 1 h after injection of 2 mg/kg b.w. of Clariscan. The endothelial transfer constant, Kps, which reflects overall vascular permeability, and the fractional plasma volume, fPV, were estimated from time-intensity curves acquired from three separate regions of interest (ROIs): whole tumor, a permeability hot spot, and a blood volume hot spot. Kps and fPV were compared to the results of histologic tumor grading (Scarff-Bloom-Richardson, SBR) and microvascular density, MVD. RESULTS: A statistically significant correlation between the MR-derived Kps parameters and the SBR score was obtained for the whole tumor ROI (R = 0.70), and for the permeability hot spot ROIs (R = 0.67). A correlation between fPV and SBR was detected for the blood volume hot spot ROIs (R = 0.48). There was no statistically significant correlation between Kps or fPV with MVD. CONCLUSION: The results support the hypothesis that dynamic MR with the intravascular contrast agent Clariscan may be used for non-invasive tumor grading.

pH-sensitive paramagnetic liposomes as MRI contrast agents: in vitro feasibility studies.

A novel type of pH-sensitive paramagnetic contrast agent is introduced; a low molecular weight gadolinium (Gd) chelate (GdDTPA-BMA) encapsulated within pH-sensitive liposomes. The in vitro relaxometric properties of the liposomal Gd chelate were shown to be a function of the pH in the liposomal dispersion and the membrane composition. Only a minor pH-dependency of the T1 relaxivity (r1) was observed for liposomal GdDTPA-BMA composed of the unsaturated lipids dioleoyl phosphatidyl ethanolamine (DOPE) and oleic acid (OA). On the other hand, the r1 of GdDTPA-BMA encapsulated within saturated dipalmitoyl phosphatidyl ethanolamine/palmitic acid (DPPE/PA) liposomes demonstrated a strong pH-dependency. At physiological pH and above, the r1 of this system was significantly lowered compared to that of non-liposomal Gd chelate, which was explained by an exchange limited relaxation process. Lowering the pH below physiological value, however, gave a sharp and 6-7 fold increase in r1, due to liposome destabilisation and subsequent leakage of entrapped GdDTPA-BMA. The pH-sensitivity of the DPPE/PA liposome system was confirmed in an in vitro magnetic resonance imaging (MRI) phantom study.

Pre-clinical results with Clariscan (NC100150 Injection); experience from different disease models.

A superparamagnetic nanoparticle (NC100150 Injection) was investigated in two different animal models; renal perfusion in pigs and tumour imaging in mice. In the pig model, qualitative first-pass perfusion maps following a bolus injection of NC100150 Injection enabled good visualisation of hypoperfused regions of the renal cortex following partial ligation of the renal artery. High temporal resolution was found to be essential to accurately capture the first passage of the contrast agent through the kidney due to the very rapid blood flow in normal renal cortex. In the tumour model (LS174T cells implanted in nude mice), NC100150 Injection was found to cause a gradual (over 60 min) signal increase on T1-w images in part of the tumours which was attributed to contrast agent leakage from the vascular space to the extravascular space in areas of increased capillary permeability. This observation is consistent with previous reports on the molecular cut-off size for vascular extraction for this tumour cell line. The specific enhancement of tumour tissue suggest potential utility of NC100150 Injection as an angiogenesis marker.