Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Exercise testing remains a remarkably durable and versatile tool that provides valuable diagnostic and prognostic information regarding patients with cardiovascular and pulmonary disease. Exercise testing has been available for more than a half century and, like many other cardiovascular procedures, has evolved in its technology and scope. When combined with exercise testing, adjunctive imaging modalities offer greater diagnostic accuracy, additional information regarding cardiac structure and function, and additional prognostic information. Similarly, the addition of ventilatory gas exchange measurements during exercise testing provides a wide array of unique and clinically useful incremental information that heretofore has been poorly understood and underutilized by the practicing clinician. The reasons for this are many and include the requirement for additional equipment (cardiopulmonary exercise testing [CPX] systems), personnel who are proficient in the administration and interpretation of these tests, limited or absence of training of cardiovascular specialists and limited training by pulmonary specialists in this technique, and the lack of understanding of the value of CPX by practicing clinicians.

Modern CPX systems allow for the analysis of gas exchange at rest, during exercise, and during recovery and yield breath-by-breath measures of oxygen uptake (Vo2), carbon dioxide output (Vco2), and ventilation (Ve). These advanced computerized systems provide both simple and complex analyses of these data that are easy to retrieve and store, which makes CPX available for widespread use. These data can be readily integrated with standard variables measured during exercise testing, including heart rate, blood pressure, work rate, electrocardiography findings, and symptoms, to provide a comprehensive assessment of exercise tolerance and exercise responses. CPX can even be performed with adjunctive imaging modalities for additional diagnostic assessment. Hence, CPX offers the clinician the ability to obtain a wealth of information beyond standard exercise electrocardiography testing that when appropriately applied and interpreted …

Clinician’s Guide to Cardiopulmonary Exercise Testing in Adults A Scientific Statement From the American Heart Association

Computer-aided drug discovery/design methods have played a major role in the development of therapeutically important small molecules for over three decades. These methods are broadly classified as either structure-based or ligand-based methods. Structure-based methods are in principle analogous to high-throughput screening in that both target and ligand structure information is imperative. Structure-based approaches include ligand docking, pharmacophore, and ligand design methods. The article discusses theory behind the most important methods and recent successful applications. Ligand-based methods use only ligand information for predicting activity depending on its similarity/dissimilarity to previously known active ligands. We review widely used ligand-based methods such as ligand-based pharmacophores, molecular descriptors, and quantitative structure-activity relationships. In addition, important tools such as target/ligand data bases, homology modeling, ligand fingerprint methods, etc., necessary for successful implementation of various computer-aided drug discovery/design methods in a drug discovery campaign are discussed. Finally, computational methods for toxicity prediction and optimization for favorable physiologic properties are discussed with successful examples from literature.

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Computational Methods in Drug Discovery

Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (BOLD) signal changes that demonstrated at least eight characteristics of CSD, time-locked to percept/onset of the aura. Initially, a focal increase in BOLD signal (possibly reflecting vasodilation), developed within extrastriate cortex (area V3A). This BOLD change progressed contiguously and slowly (3.5 ± 1.1 mm/min) over occipital cortex, congruent with the retinotopy of the visual percept. Following the same retinotopic progression, the BOLD signal then diminished (possibly reflecting vasoconstriction after the initial vasodilation), as did the BOLD response to visual activation. During periods with no visual stimulation, but while the subject was experiencing scintillations, BOLD signal followed the retinotopic progression of the visual percept. These data strongly suggest that an electrophysiological event such as CSD generates the aura in human visual cortex.

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Mechanisms of migraine aura revealed by functional MRI in human visual cortex

Background and Purpose— The National Institutes of Health (NIH) estimates that stroke costs now exceed $45 billion per year. Stroke is the third leading cause of death and one of the leading causes of adult disability in North America, Europe, and Asia. A number of well-designed randomized stroke trials and case series have now been reported in the literature to evaluate the safety and efficacy of thrombolytic therapy for the treatment of acute ischemic stroke. These stroke trials have included intravenous studies, intra-arterial studies, and combinations of both, as well as use of mechanical devices for removal of thromboemboli and of neuroprotectant drugs, alone or in combination with thrombolytic therapy. At this time, the only therapy demonstrated to improve outcomes from an acute stroke is thrombolysis of the clot responsible for the ischemic event. There is room for improvement in stroke lysis studies. Divergent criteria, with disparate reporting standards and definitions, have made direct compariso...

Trial Design and Reporting Standards for Intra-Arterial Cerebral Thrombolysis for Acute Ischemic Stroke

Regional changes in brain gray and white matter in patients with schizophrenia demonstrated with voxel-based analysis of MRI

Multivariate voxel-based morphometry successfully differentiates schizophrenia patients from healthy controls.

Our purpose was to evaluate diffusion-weighted (DW) echo-planar MRI in differentiating between brain abscess and tumour. We examined two patients with surgically confirmed pyogenic brain abscess and 18 with metastatic brain tumours or high-grade glioma, using a 1.5 T system. The apparent diffusion coefficient (ADC) of each necrotic or solid contrast-enhancing lesion was measured with two different b values (20 and 1200 s/mm2). All capsule-stage brain abscesses (4 lesions) and zones of cerebritis (2 lesions) were identified on high-b-value DWI as markedly high-signal areas of decreased ADC (range, 0.58–0.70 [(10–3 mm2/s; mean, 0.63)]). All cystic or necrotic portions of brain tumours (14 lesions) were identified on high-b-value DWI as low-signal areas of increased ADC (range, 2.20–3.20 [(10–3 mm2/s; mean, 2.70)]). Solid, contrast-enhancing portions of brain tumours (19 lesions) were identified on high-b-value DWI as high-signal areas of sightly decreased or increased ADC (range, 0.77–1.29 [(10–3 mm2/s; mean, 0.94)]). Our preliminary results indicate that DW echo-planar MRI be used for distinguishing between brain abscess and tumour.

Role of diffusion-weighted echo-planar MRI in distinguishing between brain abscess and tumour: a preliminary report

Common abnormalities within the schizophrenia spectrum may be essential for the pathogenesis of schizophrenia, but additional pathological changes may be required for the development of full-blown schizophrenia. Clarifying the neurobiological similarities and differences between established schizophrenia and a milder form of schizophrenia spectrum disorder would potentially discriminate the pathophysiological mechanisms underlying the core features of the schizophrenia spectrum from those associated with overt psychosis. High-resolution MRIs were acquired from 25 patients with schizotypal disorder, 53 patients with schizophrenia and 59 healthy volunteers matched for age, gender, handedness and parental education. Volumetric measurements of the medial temporal structures and the prefrontal cortex subcomponents were performed using consecutive 1-mm thick coronal slices. Parcellation of the prefrontal cortex into subcomponents was performed according to the intrinsic anatomical landmarks of the frontal sulci/gyri. Compared with the controls, the bilateral volumes of the amygdala and the hippocampus were reduced comparably in the schizotypal and schizophrenia patients. The parahippocampal gyrus volume did not differ significantly between diagnostic groups. Total prefrontal grey matter volumes were smaller bilaterally in the schizophrenia patients than in the controls and the schizotypal patients, whereas the schizotypal patients had larger prefrontal grey matter than the controls in the right hemisphere. In the schizophrenia patients, grey matter volumes of the bilateral superior frontal gyrus, left middle frontal gyrus, bilateral inferior frontal gyrus and bilateral straight gyrus were smaller than those in the controls. The schizophrenia patients also had reduced grey matter volumes in the right superior frontal gyrus, bilateral middle frontal gyrus and right inferior frontal gyrus relative to the schizotypal patients. Compared with the controls, the schizotypal patients had larger volumes of the bilateral middle frontal gyrus and smaller volumes of the right straight gyrus. There were no significant between-group differences in volumes of the ventral medial prefrontal cortex or the orbitofrontal cortex. These findings suggest that volume reductions in the amygdala and hippocampus are the common morphological substrates for the schizophrenia spectrum, which presumably represent the vulnerability. Additional widespread involvement of the prefrontal cortex in schizophrenia may lead to the loss of inhibitory control in other brain regions and suggests (although it is not specifically be related to) its critical role in the manifestation of overt psychosis.

Hikaru Seto

Papers

Regional changes in brain gray and white matter in patients with schizophrenia demonstrated with voxel-based analysis of MRI

Multivariate voxel-based morphometry successfully differentiates schizophrenia patients from healthy controls.

Role of diffusion-weighted echo-planar MRI in distinguishing between brain abscess and tumour: a preliminary report

Differential contributions of prefrontal and temporolimbic pathology to mechanisms of psychosis

Decreased volume and increased asymmetry of the anterior limb of the internal capsule in patients with schizophrenia.