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Voxel-based morphometry has recently been used successfully to detect gray matter volume reductions in schizophrenic patients. The aim of the present study was to confirm the findings on gray-matter changes and to complement these by applying the methodology to CSF-differences. Also, we wanted to determine whether a correlation exists between a clinically defined parameter of disease severity and brain morphology in schizophrenic patients. We investigated 48 schizophrenic patients and compared them with 48 strictly age- and sex-matched controls. High-resolution whole-brain MR-images were segmented and analyzed using SPM99. In a further analysis, the covariate effect of the global assessment of functioning-score (GAF) was calculated. Main findings were (i) left-dominant frontal, temporal, and insular GM-reductions and (ii) GM-increases in schizophrenic patients in the right basal ganglia and bilaterally in the superior cerebellum; (iii) CSF-space increases in patients complementary to some GM-reductions; (iv) a correlation between the GAF-score and local GM-volume in the left inferior frontal and inferior parietal lobe of schizophrenic patients. This study confirms and extends some earlier findings on GM-reduction and detected distinct GM-increases in schizophrenic patients. These changes were corroborated by complementary CSF-increases. Most importantly, a correlation could be established between two particular gray matter-regions and the overall disease severity, with more severely ill patients displaying a local GM-deficit. These findings may be of potentially large importance for both the future interpretation and design of neuroimaging studies in schizophrenia and the further elucidation of possible pathophysiological processes occurring in this disease.

Subcortical white matter hyperintensities (WMH) and small cystic lesions are the radiologic hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy causing stroke in young adults. To further characterize the cerebral pathology in vivo we analyzed metabolite concentrations in normal and abnormal appearing brain tissue using single and multiple voxel proton MR spectroscopy (1H-MRS and 1H-MRSI).

Functional magnetic resonance imaging was used to investigate neural activity during the judgment of visual stimuli in two groups of experiments using seven and five normal subjects. The subjects were given tasks designed differentially to involve orthographic (more generally, visual form), phonological, and lexico-semantic processes. These tasks included the judgments of whether a line was horizontal, whether a pseudocharacter or pseudocharacter string included a horizontal line, whether a Japanese katakana (phonogram) character or character string included a certain vowel, or whether a character string was meaningful (noun or verb) or meaningless. Neural activity related to the visual form process was commonly observed during judgments of both single real-characters and single pseudocharacters in lateral extrastriate visual cortex, the posterior ventral or medial occipito-temporal area, and the posterior inferior temporal area of both hemispheres. In contrast, left-lateralized activation was observed in the latter two areas during judgments of real- and pseudo-character strings. These results show that there is no katakana “word form center” whose activity is specific to real words. Activation related to the phonological process was observed, in Broca's area, the insula, the supramarginal gyrus, and the posterior superior temporal area, with greater activation in the left hemisphere. These activation foci for visual form and phonological processes of katakana also were reported for the English alphabet in previous studies. The present activation showed no additional areas for contrasts of noun judgment with other conditions and was similar between noun and verb judgment tasks, suggesting two possibilities: no strong semantic activation was produced, or the semantic process shared activation foci with the phonological process. Hum. Brain Mapping 8:44–59, 1999. © 1999 Wiley-Liss, Inc.

Functional magnetic resonance imaging was used to investigate neural activity during the judgment of visual stimuli in two groups of experiments using seven and five normal subjects. The subjects were given tasks designed differentially to involve orthographic (more generally, visual form), phonological, and lexico‐semantic processes. These tasks included the judgments of whether a line was horizontal, whether a pseudocharacter or pseudocharacter string included a horizontal line, whether a Japanese katakana (phonogram) character or character string included a certain vowel, or whether a character string was meaningful (noun or verb) or meaningless. Neural activity related to the visual form process was commonly observed during judgments of both single real‐characters and single pseudocharacters in lateral extrastriate visual cortex, the posterior ventral or medial occipito‐temporal area, and the posterior inferior temporal area of both hemispheres. In contrast, left‐lateralized activation was observed in the latter two areas during judgments of real‐ and pseudo‐character strings. These results show that there is no katakana “word form center” whose activity is specific to real words. Activation related to the phonological process was observed, in Broca's area, the insula, the supramarginal gyrus, and the posterior superior temporal area, with greater activation in the left hemisphere. These activation foci for visual form and phonological processes of katakana also were reported for the English alphabet in previous studies. The present activation showed no additional areas for contrasts of noun judgment with other conditions and was similar between noun and verb judgment tasks, suggesting two possibilities: no strong semantic activation was produced, or the semantic process shared activation foci with the phonological process. Hum. Brain Mapping 8:44–59, 1999. © 1999 Wiley‐Liss, Inc.

We review the mechanisms by which liposomal contrast agents-solutions of liposomes that entrap and deliver (usually paramagnetic) contrast agent into specific tissues-cause a desired enhancement of the bulk relaxation rate in tissues. The relaxation-enhancing action for transverse magnetization can be most generally explained by exchange (inner sphere relaxation) and diffu-sional dephasing (outer sphere relaxation). Simple analytic expressions for inner and outer sphere relaxation mechanisms are presented. At typical MRI field strengths (≤ 1T) longitudinal magnetization is affected only by inner sphere relaxation. For typical liposomal preparations the transverse magnetization relaxation is also dominated by the inner sphere mechanism. For rather low effective concentrations (2mM) of Gd(DTPA)2-, a relaxation rate enhancement of several Hertz is typically achieved, and the rate increases linearly with the concentration of liposomes. The inner sphere model presented here is similar to recent descriptions which significantly generalize earlier models which have not taken into account the finite lifetime of water inside the liposomes. The present model describes how the permeability, the relative size and the relax-ivity of the entrapped contrast agent affect the bulk relaxivity of the tissue to which liposomal contrast agents have been introduced. Outer sphere relaxation plays a minor role and is comparable to inner sphere relaxation only for larger (diameters ≤ 500 nm), reasonably impermeable (Pd≤ < 10-3 cm/s) liposomes for which the bulk rate enhancement is rather low-about one Hertz. A notable exception occurs for giant (diameters ≤ 10μm), multivesicular liposomes where the bulk rates can be many times higher. Simulations have been carried out for the purpose of investigating the simultaneous action of inner and outer sphere relaxation. The simulations reveal the expected dependence of outer sphere relaxation time on the echo time, but they consistently predict a relaxation rate about twice as high as what the outer sphere theory predicts. In the realm of liposomes studied here, the simulations imply an independence of the inner and outer sphere relaxation mechanisms; i. e., relaxation enhancements can be calculated independently and simply added.

Stromelysin-3 (ST-3) mRNA expression was studied in 28 colorectal carcinomas and compared with that of adjacent nontumorous tissue. By Northern blot analysis, levels of ST-3 mRNA were significantly increased in the carcinomas compared with nontumorous tissue. No significant correlation with ST-3 expression was seen with degree of invasion, nodal or distant metastases, or histologic grade. In situ hybridization of nontumorous tissue showed no significant ST-3 expression. In tumor tissue, ST-3 mRNA was localized adjacent to colon carcinoma cells in irregular foci within the stroma. No significant difference in ST-3 expression was found between the center and periphery of the colon tumors. Most of the colon carcinomas (26 of 28) induced an expression of ST-3 in the directly adjacent stroma. No significant correlation between ST-3 mRNA expression and tumor stage and grade was seen. By Northern blot, we also saw expression of ST-3 in non-carcinomatous tissue, further supporting the concept that ST-3 expression is a tumor-induced but not a tumor-specific phenomenon.

1. Using functional magnetic resonance imaging, we investigated the neural correlates of sequential procedural learning. During the test scans the subjects learned a new sequence (position or color) of button presses; during the control scans they pressed the buttons in any order. The comparison of the test and control scans was expected to reveal the neural activities related to learning, not sensory-motor processes. 2. We found that a localized area in what we regard to be the human homologue of the presupplementary motor area (pre-SMA) was particularly active for learning of new sequential procedures (either position or color sequences), not movements per se. 3. In contrast, the SMA proper (posterior to pre-SMA) was active for the performance of sequential movements, not learning. This was shown in another paradigm in which the subjects pressed the buttons in any order in the test scans and just watched the sequence in the control scans. 4. The learning-related pre-SMA region, which was consistent across different experiments in single subjects, was identified on only one side in each subject.

In crucial cases the diagnosis of non-Hodgkin's lymphoma (NHL) still represents a challenge to the pathologist since morphological criteria do not always help to distinguish between reactive and malignant lymphoproliferations. Clonality assays are a useful supplement since monoclonal cell proliferation is strong evidence for malignancy. The polymerase chain reaction (PCR) can be utilized to establish the clonal origin of B-or T-cell lymphocyte populations by amplification of rearranged immunoglobulin and T-cell receptor (TCR) genes. In the present study DNA was isolated from a variety of neoplastic and nonneoplastic formalin-fixed, paraffin-embedded lymph nodes (n=62), cutaneous tissue (n=9), samples of miscellaneous origin (n=11), and, reported here for the first time, decalcified bone marrow samples (n=35). These samples were submitted to PCR-based assays directed against the immunoglobulin heavy-chain (IgH), immunoglobulin ? light-chain (IgL?), and TCR? chain genes. The impact of various decalcifying agents on the ability to amplify DNA was investigated by PCR-based amplification of a single copy gene. Buffered and nonbuffered EDTA was found not to impede amplification of DNA fragments up to 300 bp in length. In lymph node and cutaneous specimens monoclonality was detected in 83% of B-NHL cases using a seminested PCR approach for the amplification of IgH, whereas the same approach gave rise to monoclonal bands in 80% of bone marrow samples. The subsequent amplification of IgL? helped to raise the sensitivity of detection to 94%. Monoclonality was detected in seven of nine T-cell NHLs by amplification of TCR?. Most of the false-negative results were related to DNA extracted from centroblastic-centrocytic lymphoma and lymphoplasmocytic immunocytoma (37% negative each). PCR-based rearrangement analysis of immunoglobulin and TCR chain genes should be used in diagnostic pathology for cases which are histopathologically and immunohistochemically questionable. The application of clonality assays to bone marrow samples previously decalcified with EDTA provides a new tool for the detection of minimal residual disease.

A new locus for restless legs syndrome (RLS3) was identified on chromosome 9p24-22. The authors analyzed transmission disequilibrium tests (TDTs) and affecteds-only linkage analysis in one large family of Bavarian origin, taking into account age at onset. Pvalues were 0.0054 for marker D9S1810 for TDT and 0.0009 for the affecteds-only linkage analysis, providing a confirmation of RLS3. This study narrows the region containing the autosomal dominant RLS3 locus to 11.1 cM (16.6 Mbp).