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Connective tissue growth factor (CTGF) is involved in the pathogenesis of various fibrotic disorders. However, its role in the heart is not clear. To investigate the role of CTGF in regulating the development of cardiac fibrosis and heart failure, we subjected mice to thoracic aortic constriction (TAC) or angiotensin II infusion, and antagonized the function of CTGF with CTGF monoclonal antibody (mAb). After 8 weeks of TAC, mice treated with CTGF mAb had significantly better preserved left ventricular (LV) systolic function and reduced LV dilatation compared with mice treated with control immunoglobulin G. CTGF mAb-treated mice exhibited significantly smaller cardiomyocyte cross-sectional area and reduced expression of hypertrophic marker genes. CTGF mAb treatment reduced the TAC-induced production of collagen 1 but did not significantly attenuate TAC-induced accumulation of interstitial fibrosis. Analysis of genes regulating extracellular matrix proteolysis showed decreased expression of plasminogen activator inhibitor-1 and matrix metalloproteinase-2 in mice treated with CTGF mAb. In contrast to TAC, antagonizing the function of CTGF had no effect on LV dysfunction or LV hypertrophy in mice subjected to 4-week angiotensin II infusion. Further analysis showed that angiotensin II-induced expression of hypertrophic marker genes or collagens was not affected by treatment with CTGF mAb. In conclusion, CTGF mAb protects from adverse LV remodeling and LV dysfunction in hearts subjected to pressure overload by TAC. Antagonizing the function of CTGF may offer protection from cardiac end-organ damage in patients with hypertension. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the technical quality of 3D coronary MR angiography (CMRA) with navigator echo and the consistency of image interpretation in repeated imaging sessions. Fourteen subjects underwent CMRA, 10 of whom were imaged twice. The coronary arteries (96 segments) were analyzed twice for hemodynamically significant stenoses. Signal-to-noise and contrast-to-noise ratios varied considerably between the two imagings. Fat saturation was poor or satisfactory in 37%; in 15% of the slabs, the severity of artifacts was moderate; and the overall quality was good to excellent in only 42% of the imagings. The intraobserver reproducibility was good (kappa = 0.54), but the consistency of interpretation for repeated CMRA was only satisfactory (kappa = 0.43). Sensitivities of 84 and 84% and specificities of 70 and 62% were obtained for the two readings. Although the reproducibility of image reading is good, 3D CMRA with navigator echo provides only fair technical consistency, and the frequently compromised image quality impairs the clinical utility of this technique.

Background and Purpose: More effective imaging methods are needed to overcome the limitations of CT in the investigation of treatments for acute ischemic stroke. Diffusion-weighted MRI (DWI) is sensitive in detecting infarcted brain tissue, whereas perfusion-weighted MRI (PWI) can detect brain perfusion in the same imaging session. Combining these methods may help in identifying the ischemic penumbra, which is an important concept in the hemodynamics of acute stroke. The purpose of this study was to determine whether combined DWI and PWI in acute (<24 hours) ischemic stroke can predict infarct growth and final size., Methods: Forty-six patients with acute ischemic stroke underwent DWI and PWI on days 1, 2, and 8. No patient received thrombolysis. Twenty-three patients underwent single-photon emission CT in the acute phase. Lesion volumes were measured from DWI, SPECT, and maps of relative cerebral blood flow calculated from PWI., Results: The mean volume of infarcted tissue detected by DWI increased from 46.1 to 75.6 cm(3) between days 1 and 2 (P<0.001; n=46) and to 78.5 cm(3) after 1 week (P<0.001; n=42). The perfusion-diffusion mismatch correlated with infarct growth (r=0. 699, P<0.001). The volume of hypoperfusion on the initial PWI correlated with final infarct size (r=0.827, P<0.001). The hypoperfusion volumes detected by PWI and SPECT correlated significantly (r=0.824, P<0.001)., Conclusions: Combined DWI and PWI can predict infarct enlargement in acute stroke. PWI can detect hypoperfused brain tissue in good agreement with SPECT in acute stroke.

Rationale and Objectives: The authors compare the usefulness of intravascular ultrasound (IVUS) and magnetic resonance imaging (MRI) for quantitation of atherosclerosis in hyperlipidemic rabbits, correlated with histopathology., Methods: Magnetic resonance imaging with T1- and T2-weighted spin echo sequences and three-dimensional time-of-flight MR angiography of the abdominal aorta was performed on seven rabbits using a 1.5 T MR imager and a standard head coil. X-ray angiography and IVUS examination (3.5 F/30 MHz imaging catheter) was performed via carotid artery access., Results: Time-of-flight MR angiography source images provided the best resolution and plaque-lumen contrast in visual comparison between the different MRI sequences. Intra- and interobserver reproducibilities of the lesion thickness and area measurements were similar in IVUS and MRI (Pearson correlations 0.52-0.97; P < 0.01). The measurements from IVUS and MRI correlated closely with each other as well as with those made from histopathologic specimens (Pearson correlations 0.50-0.79; P < 0.001). The measurements from IVUS were somewhat more accurate than those made from MRI., Conclusions: Both MRI and IVUS with clinically available imaging equipments are feasible and accurate for the quantitation of experimental atherosclerosis of rabbit aorta.

Purpose: Our goal was to evaluate CT angiography (CTA) in diagnosing renal artery stenosis (RAS)., Method: Thirty-seven patients underwent digital subtraction angiography (DSA) and CTA. Visual interpretation and stenosis measurements were made from maximum intensity projection (MIP) and multiplanar reformation (MPR) laser film prints of 78 renal arteries., Results: Visual reading of MIP films showed good diagnostic performance by receiver operating characteristic curve analysis, with 100% sensitivity in the assessment of > or = 50% RAS but only 42-54% specificity (overall accuracy 60-75%). The false-positive rate decreased when MIP and MPR films were read together, but the excess of false negatives among the calcified lesions disabled this diagnostic algorithm. Combining visual interpretation of MIP films with quantitative measurements yielded the best diagnostic performance: 92% sensitivity, 80% specificity, and 84% overall accuracy. Renal cortical enhancement measurements (26 patients) had 81% overall accuracy., Conclusion: The overall accuracy of CTA with MIP film reading can be enhanced by quantitative measurement of stenosis or reviewing MPRs.

We have studied a possible role of cholecystokinin (CCK) in regulating adrenal medullary function. Caerulein (10(-10)-10(-7) M), a CCK receptor agonist, increased formation of inositol phosphates in primary cultured bovine adrenal medullary (BAM) chromaffin cells in a concentration-dependent manner. The effect of caerulein was antagonized by devazepide, a selective CCKA-receptor antagonist, but not by L-365.260, a selective CCKB-receptor antagonist. These results suggest that BAM cells possess functional CCK receptors of the CCKA-subtype. Stimulation of these receptors with caerulein activates a signal transduction pathway via phospholipase C. CCK may regulate catecholamine release in BAM cells.

We present a novel method to integrate in vivo nuclear magnetic resonance spectroscopy (MRS) information into the clinical diagnosis of brain tumours. Water-suppressed 1H MRS data were collected from 33 patients with brain tumours and 28 healthy controls in vivo. The data were treated in the time domain for removal of residual water and a region from the frequency domain (from 3.4 to 0.3 p.p.m.) together with the unsuppressed water signal were used as inputs for artificial neural network (ANN) analysis. The ANN distinguished tumour and normal tissue in each case and was able to classify benign and malignant gliomas as well as other brain tumours to match histology in a clinically useful manner with an accuracy of 82%. Thus the present data indicate existence of tumour tissue-specific metabolite phenotypes that can be detected by in vivo 1H MRS. We believe that a user-independent ANN analysis may provide an alternative method for tumour classification in clinical practice.

We analyzed hippocampal volumes and T2 relaxation times by MRI from 78 control subjects, 24 patients with temporal lobe epilepsy, and 55 patients with Alzheimer's disease (AD). In the epilepsy group, the hippocampal volumes were 27% smaller than in control subjects (p < 0.001). The T2 relaxation times were prolonged (8 to 20 ms compared with control subjects) in the head, body, and tail portions of the hippocampus on the focal side (p < 0.01) and also on the contralateral side (p < 0.05) compared with control subjects. In the epilepsy group, the prolongation of T2 relaxation time correlated inversely with the hippocampal volume (p < 0.05). In the AD group, the hippocampal volumes were 35% smaller than in control subjects (p < 0.01). The T2 relaxation times were slightly prolonged (5 to 6 ms) in the head and tail portions of the right hippocampus (p < 0.01), but the T2 relaxation times did not correlate with the hippocampal volumes. These data show that the degree of prolongation of T2 relaxation time is associated with severity of hippocampal atrophy in temporal lobe epilepsy but not in AD.

Hippocampal atrophy detected by volumetric MRI is a sensitive feature of early Alzheimer's disease (AD), but there are no studies evaluating hippocampal atrophy by MR volumetry in other dementing diseases. We therefore compared hippocampal volumes in a total of 113 subjects: 50 patients with mild to moderate AD, 9 patients with vascular dementia (VaD), 12 patients with idiopathic Parkinson's disease (PD) without dementia, 8 patients with PD and dementia (PDD), and 34 elderly control subjects. Thin, coronal, contiguous images were obtained by a 1.5-T MR imager. All patient groups had significantly smaller volumes of the hippocampus compared with the control group. In the PDD group, the absolute volumes were even smaller than in the AD group. In the PD group, the volumes were diminished to a lesser but significant extent. The volumes in the VaD group varied: of nine patients, two had no atrophy, three had unilateral, and four had bilateral atrophy. We postulate that hippocampal atrophy does not seem to be a specific phenomenon of dementia in AD but also occurs in VaD and PDD, and even in PD when no dementia is present. However, coexistence of AD pathology in our PD and VaD patients cannot be ruled out. Further studies with access to neuropathologic data are needed.

We evaluated the ability of MRI of the amygdala to diagnose early Alzheimer's disease (AD). The volume of the amygdala was measured in 54 patients with probable AD, 38 subjects with age-associated memory impairment (AAMI), 34 cognitively normal elderly controls (OC) and 20 young controls (YC). The amygdala was atrophied in all the elderly study groups with atrophy being strongest in the AD group (p < 0.0001). The OC and AAMI groups differed from the YC group (p < 0.05) but not from each other. There was a major overlap between the study groups. The volumes also correlated with age (p < 0.0001) and gender (p < 0.001). A correct classification was achieved in 74% of AD patients and the non-demented elderly subjects. Thus, MRI of amygdala fails to diagnose AD accurately.

It is a matter of dispute whether or not recurrent epileptic seizures cause neuronal damage in the human brain. We approached this question by measuring the volumes of the amygdala, hippocampus and parahippocampal gyrus with magnetic resonance imaging in 15 controls, 13 unmedicated patients with newly diagnosed epilepsy and 16 patients with chronic drug-refractory epilepsy. In all patients, the seizure origin was in the temporal lobe region and the seizure aetiology was unknown. Newly diagnosed epilepsy patients with seizure lateralization on the left had increased hippocampal right-left difference (p < 0.01) and right/left ratio (p < 0.05) compared with controls. Patients with chronic epilepsy and lateralization on the left had increased hippocampal right-left difference (p < 0.05) and right/left ratio (p < 0.05) compared with controls. In this patient group, the volume of the left hippocampus was 16% smaller than in controls (p < 0.01). The rostral portion of the parahippocampal gyrus was 12% smaller than in controls (p < 0.01). In chronic epilepsy patients with lateralization on the right, we found a statistically non-significant decrease (13%) in the right hippocampal volume compared with controls. In this patient group, the amygdaloid right-left difference (p < 0.05) and right/left ratio (p < 0.05) were decreased compared with controls. The present cross-sectional study provides evidence that mild hippocampal damage is already present in the early stages of epilepsy. Hippocampal damage is more severe in patients with a long history of recurrent generalized seizures.(ABSTRACT TRUNCATED AT 250 WORDS)

We used proton magnetic resonance spectroscopy (1H MRS) to determine concentrations of N-acetylaspartate (NAA), creatine and choline in vivo (63 MHz) and in vitro (400 MHz) in seven patients undergoing surgical treatment of intractable temporal lobe epilepsy (TLE). Nine healthy volunteers were used as controls for in vivo MRS. NAA concentrations in vivo on the ipsilateral and contralateral sides were 6.5 +/- 1.3 (s.d.) and 7.9 (+/- 2.1) mmol l-1, respectively and 8.6 (+/- 0.8) mmol l-1 in the volunteers. NAA concentration in vitro was 3.2 (+/- 0.9) mumol g-1 wet weight (ww) and the corresponding concentration from the macroscopically intact brain tissue was 4.7 (+/- 1.0) mumol g-1 ww. Thus, in vivo quantitative 1H MRS identified the size of seizure focus in patients with temporal lobe epilepsy.

Objective: The aim of the present study was to investigate quantitative metabolite patterns in human brain tumors by 1H nuclear MR spectroscopy (1H MRS)., Materials and Methods: Single voxel 1H MRS was used in studying metabolites in 23 primary brain tumors in vivo. The T2 relaxation times and saturation factors were determined for N-acetylaspartate (NAA), total creatine (Cr), choline-containing compounds (Cho), and water, which was used as an internal standard in computations of metabolite concentrations in vivo. Metabolites in biopsy specimens from 75 tumors were quantified by means of 1H MRS in vitro., Results: The NAA concentrations were lower in brain tumors than in normal tissue in vitro and in vivo, irrespective of the histological type. The NAA was some threefold higher in vivo than in vitro, which could be due to partial volume effect and/or contributions from other metabolites to the peak at 2.02 ppm in vivo. Ratios of Cho to Cr concentrations were elevated in tumors relative to normal brain in vivo. Absolute Cho was some 50% higher in both benign astrocytomas and oligodendrogliomas in vivo than in normal brain. However, Cho concentration in vitro was significantly higher only in pituitary adenomas than in healthy white matter. Total creatine was approximately 50% lower in malignant astrocytomas and meningiomas than in normal brain., Conclusion: It is concluded that absolute concentrations of metabolites in vivo yield a different picture of tumor metabolites than that derived from uncorrected metabolite ratios.