Diagnosis of Regional Cerebral Blood Flow Abnormalities Using Spect: Agreement between Individualized Statistical Parametric Maps and Visual Inspection by Nuclear Medicine Physicians with Different Levels of Expertise in Nuclear Neurology

INTRODUCTION:

Visual analysis is widely used to interpret regional cerebral blood flow (rCBF) SPECT images in clinical practice despite its limitations. Automated methods are employed to investigate between-group rCBF differences in research studies but have rarely been explored in individual analyses.

OBJECTIVES:

To compare visual inspection by nuclear physicians with the automated statistical parametric mapping program using a SPECT dataset of patients with neurological disorders and normal control images.

METHODS:

Using statistical parametric mapping, 14 SPECT images from patients with various neurological disorders were compared individually with a databank of 32 normal images using a statistical threshold of p<0.05 (corrected for multiple comparisons at the level of individual voxels or clusters). Statistical parametric mapping results were compared with visual analyses by a nuclear physician highly experienced in neurology (A) as well as a nuclear physician with a general background of experience (B) who independently classified images as normal or altered, and determined the location of changes and the severity.

RESULTS:

Of the 32 images of the normal databank, 4 generated maps showing rCBF abnormalities (p<0.05, corrected). Among the 14 images from patients with neurological disorders, 13 showed rCBF alterations. Statistical parametric mapping and physician A completely agreed on 84.37% and 64.28% of cases from the normal databank and neurological disorders, respectively. The agreement between statistical parametric mapping and ratings of physician B were lower (71.18% and 35.71%, respectively).

CONCLUSION:

Statistical parametric mapping replicated the findings described by the more experienced nuclear physician. This finding suggests that automated methods for individually analyzing rCBF SPECT images may be a valuable resource to complement visual inspection in clinical practice.     

Late onset bipolar disorder associated with white matter hyperintensities: a pathophysiological hypothesis

Vascular depression is, nowadays, a well-established concept in the literature. However, the possible emergence of late onset bipolar disorder in subjects with no antecedents of mood disorder or after a chronic or recurrent course of unipolar depression constitutes a poorly studied issue, despite its importance in clinical practice. Here, we present the case of a 72-year-old female patient who began to present recurrent major depressive symptoms, resistant to pharmacological treatment, from the age of 58. Three years later, she started to present phases of mania with rapid cycling features. A brain MRI scan showed prominent white matter hyperintensities (WMH). WMH are frequently found in the elderly population, but with greater burden in individuals with hypertension and cerebrovascular disease. WMH impair cortical function and damage the cerebral tissue. WMH have been associated with adult-onset bipolar disorder and late onset depression, and are linked to a worse prognosis of both conditions. The present case report highlights the possibility that vascular-related WMH may provoke late onset bipolar disorder by damaging frontolimbic circuits implicated in the pathophysiology of mania.     

Regional gray matter abnormalities in panic disorder: a voxel-based morphometry study

Although abnormalities in brain structures involved in the neurobiology of fear and anxiety have been implicated in the pathophysiology of panic disorder (PD), relatively few studies have made use of voxel-based morphometry (VBM) magnetic resonance imaging (MRI) to determine structural brain abnormalities in PD. We have assessed gray matter volume in 19 PD patients and 20 healthy volunteers using VBM. Images were acquired using a 1.5 T MRI scanner, and were spatially normalized and segmented using optimized VBM. Statistical comparisons were performed using the general linear model. A relative increase in gray matter volume was found in the left insula of PD patients compared with controls. Additional structures showing differential increases were the left superior temporal gyrus, the midbrain, and the pons. A relative gray matter deficit was found in the right anterior cingulate cortex. The insula and anterior cingulate abnormalities may be relevant to the pathophysiology of PD, since these structures participate in the evaluation process that ascribes negative emotional meaning to potentially distressing cognitive and interoceptive sensory information. The abnormal brain stem structures may be involved in the generation of panic attacks.     

Voxel-based morphometry in Alzheimer's disease

Recent morphometric MRI studies have investigated brain volume abnormalities associated with the diagnosis of Alzheimer's disease (AD) using voxel-based morphometry (VBM). This technique allows the assessment of gray matter volumes in subjects with AD or related conditions compared with healthy controls in an automated fashion, across the whole brain. This article reviews VBM findings related to different AD stages and its prodrome, mild cognitive impairment. These findings include not only gray matter deficits in medial temporal structures as seen in former MRI studies of AD conducted using manual region-of-interest measurements, but also volume changes in several other brain regions not assessed in previous MRI studies. We also discuss potential applications of VBM to improve AD diagnostic accuracy in routine clinical practice. Finally, we highlight future research directions in this field, including: investigations on the relationship between VBM findings of multifocal gray matter deficits and changes in white matter tracts that interconnect such regions; the need for population-based VBM studies using large AD samples; and the potential of studies combining VBM measurements with other potential biological markers (such as brain imaging indices of amyloid-beta deposition and cerebrospinal fluid AD markers) to further advance our knowledge about the physiopathology of AD.     

A procedure for the isolation of asbestos bodies from lung tissue by exploiting their magnetic properties: a new approach to asbestos body study

The role of asbestos bodies (and associated proteinacious coating) in asbestos associated diseases is not well understood. Currently employed methods of isolation of these bodies employ harsh chemicals that lead to destruction of their proteinacious coating. In this work a method was developed that enabled the purification of whole, integral, unmodified asbestos bodies (AB) by exploiting their magnetic properties. Albumin and ferritin were found to be the major proteins associated with AB isolated from lung tissue of mesothelioma patients. Magnetically isolated AB were shown to be cytotoxic and to activate free radical production from inflammatory cells at a higher extent than that induced by bodies obtained by chemical digestion. The finding that hypochlorite-treated AB induce DNA damage, while AB obtained by the method described in this article failed to do so, together with the differential behavior of these bodies toward inflammatory cells, suggests that native asbestos bodies should be used to investigate the pathogenetic role of these structures.     

The p53 gene in patients under the age of 40 with gastric cancer: mutation rates are low but are associated with a cardiac location.

BACKGROUND: Determining both the frequency and the spectrum of p53 gene mutation in young patients with gastric cancer might provide clues to the host related genetic mechanism(s) in gastric carcinogenesis. PATIENTS AND METHODS: p53 mutations were assessed (by means of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), followed by DNA sequencing) in a cohort of 105 consecutive Italian patients in whom gastric cancer was ascertained before the age of 41. RESULTS: A low prevalence of p53 mutations (eight of 105) was observed, with no significant difference between intestinal (three of 31; 10%) and diffuse (five of 74; 7%) phenotypes. A significantly higher prevalence of p53 mutations was associated with the cardiac location (odds ratio, 7.09; confidence interval, 1.56 to 32.11). In all but one case, p53 mutations were associated with a stage higher than I. All eight mutations were located at CpG sites, where G : C to A : T transitions have been associated with frequent methylation at the C5 position of cytosine. CONCLUSIONS: These findings show that, unlike what has been consistently demonstrated in the general population, p53 mutations are uncommon in gastric cancer occurring in young patients, and in such patients, p53 alterations are significantly associated with the cardiac location.     

Salmeterol improves fluid clearance from alveolar-capillary membrane in COPD patients: a pilot study

The cardiovascular component associated with chronic obstructive pulmonary disease (COPD) plays a major role in disease prognosis, accounting for 25% of the deaths. Experimental and initial clinical data suggest that beta-adrenergic agonists accelerate fluid clearance from the alveolar airspace, with potentially positive effects on cardiogenic and noncardiogenic pulmonary oedema. This pilot study investigated the acute effects of the long-acting beta-2 agonist, salmeterol, on alveolar fluid clearance after rapid saline intravenous infusion by evaluating diffusive and mechanical lung properties. Ten COPD and 10 healthy subjects were treated with salmeterol or placebo 4 h before the patient’s mechanical and diffusive lung properties were measured during four non consecutive days, just before and after a rapid saline infusion, or during a similar period without an infusion.ResultsIn both COPD and healthy subjects, rapid saline infusion with placebo or salmeterol premedication lead to a significant decrease in diffusion capacity for carbon monoxide (DLCO) and forced expiratory volume in 1 s (FEV1). Nonetheless, salmeterol pretreatment lead to a significantly reduced gas exchange impairment caused by saline infusion (?64% of DLCO reduction compared with placebo), whereas it did not affect changes in FEV1. In the control setting with no infusion, we found no significant change in either DLCO or mechanical properties of the lung.ConclusionsSalmeterol appears to provide a protective effect, not related to bronchodilation, against an acute alveolar fluid clearance challenge secondary to lung fluid overload in COPD patients.     

Brain structural correlates of sensory phenomena in patients with obsessive–compulsive disorder

Background

Sensory phenomena (SP) are uncomfortable feelings, including bodily sensations, sense of inner tension, “just-right” perceptions, feelings of incompleteness, or “urge-only” phenomena, which have been described to precede, trigger or accompany repetitive behaviours in individuals with obsessive–compulsive disorder (OCD). Sensory phenomena are also observed in individuals with tic disorders, and previous research suggests that sensorimotor cortex abnormalities underpin the presence of SP in such patients. However, to our knowledge, no studies have assessed the neural correlates of SP in patients with OCD.

Methods

We assessed the presence of SP using the University of São Paulo Sensory Phenomena Scale in patients with OCD and healthy controls from specialized units in São Paulo, Brazil, and Barcelona, Spain. All participants underwent a structural magnetic resonance examination, and brain images were examined using DARTEL voxel-based morphometry. We evaluated grey matter volume differences between patients with and without SP and healthy controls within the sensorimotor and premotor cortices.

Results

We included 106 patients with OCD and 87 controls in our study. Patients with SP (67% of the sample) showed grey matter volume increases in the left sensorimotor cortex in comparison to patients without SP and bilateral sensorimotor cortex grey matter volume increases in comparison to controls. No differences were observed between patients without SP and controls.

Limitations

Most patients were medicated. Participant recruitment and image acquisition were performed in 2 different centres.

Conclusion

We have identified a structural correlate of SP in patients with OCD involving grey matter volume increases within the sensorimotor cortex; this finding is in agreement with those of tic disorder studies showing that abnormal activity and volume increases within this region are associated with the urges preceding tic onset.     

Longitudinal brain volumetric changes during one year in non-elderly healthy adults: a voxel-based morphometry study

Previous cross-sectional magnetic resonance imaging (MRI) studies of healthy aging in young adults have indicated the presence of significant inverse correlations between age and gray matter volumes, although not homogeneously across all brain regions. However, such cross-sectional studies have important limitations and there is a scarcity of detailed longitudinal MRI studies with repeated measures obtained in the same individuals in order to investigate regional gray matter changes during short periods of time in non-elderly healthy adults. In the present study, 52 healthy young adults aged 18 to 50 years (27 males and 25 females) were followed with repeated MRI acquisitions over approximately 15 months. Gray matter volumes were compared between the two times using voxel-based morphometry, with the prediction that volume changes would be detectable in the frontal lobe, temporal neocortex and hippocampus. Voxel-wise analyses showed significant (P < 0.05, family-wise error corrected) relative volume reductions of gray matter in two small foci located in the right orbitofrontal cortex and left hippocampus. Separate comparisons for males and females showed bilateral gray matter relative reductions in the orbitofrontal cortex over time only in males. We conclude that, in non-elderly healthy adults, subtle gray matter volume alterations are detectable after short periods of time. This underscores the dynamic nature of gray matter changes in the brain during adult life, with regional volume reductions being detectable in brain regions that are relevant to cognitive and emotional processes.