Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease.

OBJECTIVE: We compared the ability of arterial spin labeling (ASL), an MRI method that measures cerebral blood flow (CBF), to that of FDG-PET in distinguishing patients with Alzheimer disease (AD) from healthy, age-matched controls. METHODS: Fifteen patients with AD (mean age 72 ± 6 years, Mini-Mental State Examination score [MMSE] 20 ± 6) and 19 age-matched controls (mean age 68 ± 6 years, MMSE 29 ± 1) underwent structural MRI. Participants were injected with 5 mCi of FDG during pseudocontinuous ASL scan, which was followed by PET scanning. Statistical parametric mapping and regions of interest (ROI) analysis were used to compare the ability of the 2 modalities in distinguishing patients from controls. Similarity between the 2 modalities was further assessed with linear correlation maps of CBF and metabolism to neuropsychological test scores. RESULTS: Good agreement between hypoperfusion and hypometabolism patterns was observed, with overlap primarily in bilateral angular gyri and posterior cingulate. ROI results showed similar scales of functional deficit between patients and controls in both modalities. Both ASL and FDG-PET were able to distinguish neural networks associated with different neuropsychological tests with good overlap between modalities. CONCLUSIONS: Our voxel-wise results indicated that ASL-MRI provides largely overlapping information with FDG-PET. ROI analysis demonstrated that both modalities detected similar degrees of functional deficits in affected areas. Given its ease of acquisition and noninvasiveness, ASL-MRI may be an appealing alternative for AD studies.

Differences in serotonin transporter binding affinity in patients with major depressive disorder and night eating syndrome.

OBJECTIVE: We examined serotonin transporter (SERT) binding affinity using single photon emission computed tomography (SPECT) in patients with major depressive disorder (MDD) and night eating syndrome (NES). There are similarities between MDD and NES in affective symptoms, appetite disturbance, nighttime awakenings, and, particularly, response to selective serotonin reuptake inhibitors (SSRIs). METHODS: Six non-depressed patients with NES and seven patients with MDD underwent SPECT brain imaging with 123I-ADAM, a radiopharmaceutical agent selective for SERT sites. Uptake ratios of 123I-ADAM SERT binding were obtained for the midbrain, basal ganglia, and temporal lobe regions compared to the cerebellum reference region. RESULTS: Patients with NES had significantly greater SERT uptake ratios (effect size range 0.64-0.84) in the midbrain, right temporal lobe, and left temporal lobe regions than those with MDD whom we had previously studied. CONCLUSIONS: Pathophysiological differences in SERT uptake between patients with NES and MDD suggest these are distinct clinical syndromes.

FDG-PET findings in patients with galactosaemia.

Despite treatment with a galactose-restricted diet, many galactosaemia patients develop lifelong cognitive impairment, speech abnormalities and a gamut of neurological problems including cognitive impairment and tremors. No study has explored changes in cerebral glucose metabolism in patients with galactosaemia. Five patients with galactosaemia had ages ranging from 20 to 40 years (mean age 28 years) and eight similarly aged controls received brain [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. PET scans were analysed using a previously validated template methodology of regions of interest (ROIs). Count ratios for each anatomical ROI were compared between the galactosaemic patients and the healthy controls. Statistical parametric mapping (SPM) software was also used to further analyse the data. ROI analysis showed that galactosaemic patients had significant bilateral decreases in cerebral glucose metabolism in the superior temporal gyrus, medial occipital lobe, parietal lobe, cerebellum, calcarine cortex, superior frontal cortex, and superior parietal cortex when compared with controls. Significant increases were seen in the cingulate gyrus and temporal poles, bilaterally. SPM analysis revealed foci of decreased glucose metabolism in the caudate, cerebellum, precentral gyrus and cerebellar tonsils of galactosaemic patients. SPM also showed increased glucose metabolism in the subcallosal gyrus and claustrum. The results show significant abnormalities in cerebral function in patients with galactosaemia, particularly with widespread decreases in cortical metabolism. These abnormalities appear to be in brain regions that may be associated with the neuropsychological deficits in these patients. PET brain scans may be of value in galactosaemia patients to evaluate for dysfunction.

Biomarkers for early detection of Alzheimer pathology.

The increasing prevalence of Alzheimer's disease and the devastating consequences of late-life dementia motivates the drive to develop diagnostic biomarkers to reliably identify the pathology associated with this disorder. Strategies to accomplish this include the detection of altered levels of tau and amyloid in cerebrospinal fluid, the use of structural MRI to identify disease-specific patterns of regional atrophy and MRI T(1)rho to detect disease-related macromolecular protein aggregation, and the direct imaging of amyloid deposits using positron emission tomography and single photon emission computerized tomography. Success will facilitate the ability to reliably diagnose Alzheimer's disease while the symptoms of brain failure are mild and may provide objective measures of disease-modifying treatment efficacy.

[99mTc]TRODAT-1 SPECT imaging correlates with odor identification in early Parkinson disease.

BACKGROUND: In vivo imaging of the dopamine transporter with [99mTc]TRODAT-1 (TRODAT) and olfactory testing have both been proposed as potential biomarkers in Parkinson disease (PD). OBJECTIVE: To evaluate the relationship between TRODAT SPECT imaging, odor identification skills, and motor function in patients with early PD. METHODS: Twenty-four patients with a clinical diagnosis of early-stage PD (mean Hoehn & Yahr stage = 1.4) underwent TRODAT imaging, Unified PD Rating Scale (UPDRS) ratings of motor function, and administration of the University of Pennsylvania Smell Identification Test (UPSIT). Brain images were obtained using a standardized processing protocol and specific uptake ratios for striatal regions of interest were calculated. Partial correlations between the imaging indices, disease duration, UPSIT scores, and UPDRS motor scores were then calculated. RESULTS: UPSIT scores were correlated with TRODAT uptake in the striatum as a whole (r = 0.66, p = 0.001). The putamen showed the strongest correlation with the UPSIT (r = 0.74; p < 0.001). The correlation between dopamine transporter density in the caudate and UPSIT was moderate (r = 0.36, p = 0.11), but was not significant. CONCLUSIONS: Olfactory function is highly correlated with dopamine transporter imaging abnormalities in early Parkinson disease (PD). Further studies are warranted to determine whether changes over time in these two measures are also correlated in early PD.

Diagnostic accuracy of [99mTc]TRODAT-1 SPECT imaging in early Parkinson's disease.

We evaluated the diagnostic accuracy of SPECT imaging using [(99m)Tc]TRODAT-1 (TRODAT), a relatively inexpensive technetium-labeled dopamine transporter ligand, in distinguishing 29 patients with early PD from 38 healthy volunteers. Mean TRODAT uptake values were significantly decreased in the caudate (p=0.0097) and anterior and posterior putamen (p < 0.0001) of PD patients compared to controls. Using the posterior putamen as the main region of interest resulted in the greatest accuracy (sensitivity 0.79, specificity 0.92). These findings show that TRODAT imaging can accurately differentiate early PD patients from controls and has the potential to improve the diagnosis of patients with early signs of PD.

The neural basis of the complex mental task of meditation: neurotransmitter and neurochemical considerations.

Meditation is a complex mental process involving changes in cognition, sensory perception, affect, hormones, and autonomic activity. Meditation has also become widely used in psychological and medical practices for stress management as well as a variety of physical and mental disorders. However, until now, there has been limited understanding of the overall biological mechanism of these practices in terms of the effects in both the brain and body. We have previously described a rudimentary neuropsychological model to explain the brain mechanisms underlying meditative experiences. This paper provides a substantial development by integrating neurotransmitter systems and the results of recent brain imaging advances into the model. The following is a review and synthesis of the current literature regarding the various neurophysiological mechanisms and neurochemical substrates that underlie the complex processes of meditation. It is hoped that this model will provide hypotheses for future biological and clinical studies of meditation.

Brain metabolism in the cerebellum and visual cortex correlates with neuropsychological testing in patients with Alzheimer's disease.

This study was designed to measure glucose metabolic deficits in areas not typically recognized as abnormal on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans in patients with Alzheimer's disease (AD), and to correlate such findings with subtle neuropsychological impairment. FDG-PET scans on 38 AD patients with no clinical evidence of visual, spatial or motor deficits were acquired on the PET HEAD scanner 40 min following the intravenous administration of 115 microCi.kg-1 of FDG. All FDG-PET scans were analysed blindly using a region of interest (ROI) template with regions for the primary visual cortex (PVC), secondary visual cortex (SVC) and cerebellum. Counts from the ROIs of these regions were normalized to whole brain activity and the results were compared with psychometric and neuropsychological measures. A number of significant correlations were found between these structures and various neuropsychological measures (P<0.05). Specifically, there were significant correlations between clock drawing and the cerebellum activity; memory and activity in the PVC, SVC and cerebellum; social score and activity in the PVC and left cerebellum; judgement and activity in the right SVC and right PVC; and the overall Mini-Mental State Examination and activity in the PVC, SVC and cerebellum. The results of this study suggest that metabolism in areas not typically recognized as abnormal on FDG-PET scans in AD, such as the PVC, SVC and cerebellum, is correlated with deficits in neuropsychological function. This may have important clinical and pathophysiological implications in the study of AD and other illnesses of dementia.

Cerebral metabolic changes associated with Lyme disease.

There are no positron emission tomography (PET) studies reported in the literature with regards to brain metabolism and function in patients with Lyme disease. These patients frequently present with various neurological symptoms, including memory problems. We used [(18)F]fluorodeoxyglucose (FDG) PET to determine the metabolic landscape in 23 patients with Lyme disease. Images were evaluated for cortical and subcortical abnormalities by two experienced reviewers blinded to the clinical information. The most striking finding was hypometabolism in the temporal lobes in 17/23 (74%) patients. Of these, 12 had bilateral temporal lobe hypometabolism, two had left temporal lobe, and three had right temporal lobe hypometabolism. Seven of the patients with temporal lobe hypometabolism had diffuse cortical hypometabolism that included the frontal and parietal lobes. Lyme disease appears to have two primary patterns of brain involvement on FDG PET scans, specific temporal lobe hypometabolism or a diffuse cortical hypometabolism. The involvement of the temporal lobes in both patterns is likely associated with the memory disturbances described in many of these patients. Although there was no clear diagnostic pattern, and many of the defects were mild, FDG PET imaging may provide important information regarding the areas of the brain affected in patients with neurological symptoms associated with Lyme disease.

Advanced imaging of melorheostosis with emphasis on MRI.

OBJECTIVE: To describe the CT and MR imaging appearance of both osseous and extraosseous manifestations of melorheostosis. DESIGN AND PATIENTS: We retrospectively reviewed the CT (n=7) and/or MR imaging findings (n=12) of 17 patients with characteristic radiographic findings of melorheostosis (undulating cortical hyperostosis with marked uptake on radionuclide bone scintigraphy). RESULTS: CT and MR imaging revealed cortical hyperostosis as high attenuation and low signal intensity on all MR pulse sequences, respectively. Encroachment on the marrow space was seen in all cases resulting from endosteal involvement. Thirteen patients demonstrated 14 soft tissue masses with infiltrative margins in 80% of cases and seven showed extensive mineralization on CT or MR imaging (low intensity on all pulse sequences). Seven soft tissue masses were predominantly nonmineralized with intermediate signal intensity on T1-weighted and intermediate to high signal on T2-weighted MR images corresponding to vascularized fibrous tissue with variable collagen content pathologically. Enhancement after intravenous gadolinium was seen in all patients imaged with soft tissue masses (n=2). Two patients demonstrated muscle atrophy resulting from nerve involvement. CONCLUSIONS: The osseous abnormalities in melorheostosis are identical on advanced imaging and radiographs. Mineralized or nonmineralized soft tissue masses should be recognized as another manifestation of this disease as opposed to a more ominous finding, making biopsy unwarrranted.

Salter-Harris III stress fracture of the proximal first metatarsal: a case report.

An intraarticular, dorsal, proximal epiphyseal stress fracture (Salter-Harris III) of the first metatarsal was identified in a 14-year-old boy. Successful fracture healing was achieved with a rocker sole shoe modification and activity limitation.

F-18 FDG uptake in the large arteries: a new observation.

PURPOSE: The cellular components of the atherosclerotic plaque, such as macrophages, exhibits high glucose metabolic activity. The aim of this study was to show the frequency of vascular uptake and possibly to explain the significance of this finding on fluorodeoxyglucose (FDG) positron emission tomographic (PET) scans. METHODS: We evaluated the presence of FDG vascular uptake in 132 consecutive patients undergoing whole-body PET scans and 5 patients who had only lower extremity scans. The presence of vascular FDG uptake was assessed in the abdominal aorta, iliac, and proximal femoral arteries on the 132 whole-body scans, whereas only the femoral and the popliteal arteries were examined on the leg scans. The patients' ages ranged from 20 to 80 years, and they were divided into three age groups: 35 patients were younger than 40 years (group 1; mean age, 32.4 years), 48 patients were 41 to 60 years (group 2; mean age, 50.3 years), and 54 patients were older than 60 years (group 3; mean age, 70.3 years). RESULTS: Fifty percent (69 of 137) of the total population showed vascular FDG uptake in at least one vessel. Thirty-four percent (12 of 35) of group 1, 50% (24 of 48) of group 2, and 61% (33 of 54) of group 3 showed vascular wall uptake (P = 0.017 between groups 1 and 3). In addition, the correlation between the mean age of the age groups and the prevalence of FDG vascular uptake is strong (r = 0.99). CONCLUSIONS: Vascular FDG uptake is present in 50% of the patients examined for this study, with an increased prevalence in older patients. This vascular uptake might be explained by smooth muscle metabolism in the media, subendothelial smooth muscle proliferation from senescence, and the presence of macrophages within the atherosclerotic plaque. The relative contribution of these sources needs further investigation.

The measurement of regional cerebral blood flow during the complex cognitive task of meditation: a preliminary SPECT study.

This study measured changes in regional cerebral blood flow (rCBF) during the complex cognitive task of meditation using single photon emission computed tomography. Eight experienced Tibetan Buddhist meditators were injected at baseline with 7 mCi HMPAO and scanned 20 min later for 45 min. The subjects then meditated for 1 h at which time they were injected with 25 mCi HMPAO and scanned 20 min later for 30 min. Values were obtained for regions of interest in major brain structures and normalized to whole brain activity. The percentage change between meditation and baseline was compared. Correlations between structures were also determined. Significantly increased rCBF (P<0.05) was observed in the cingulate gyrus, inferior and orbital frontal cortex, dorsolateral prefrontal cortex (DLPFC), and thalamus. The change in rCBF in the left DLPFC correlated negatively (P<0.05) with that in the left superior parietal lobe. Increased frontal rCBF may reflect focused concentration and thalamic increases overall increased cortical activity during meditation. The correlation between the DLPFC and the superior parietal lobe may reflect an altered sense of space experienced during meditation. These results suggest a complex rCBF pattern during the task of meditation.

Changes in cerebral blood flow associated with premenstrual syndrome: a preliminary study.

The purpose of this study was to determine changes in regional cerebral blood flow (rCBF) associated with premenstrual syndrome (PMS). Regional CBF was examined using single photon emission computed tomography (SPECT) in seven women who sought treatment for PMS and seven control subjects. Confirmation of PMS was based on the Daily Symptom Report (DSR) of 17 common symptoms associated with PMS. A first SPECT scan was performed near the peak of premenstrual symptoms based on DSR reports from the two previous cycles. A second scan was performed in the postmenstrual period. Prior to scanning, each subject had a Hamilton Depression Rating Scale (Ham-D) obtained. Regions of interest were drawn on the images to generate mean counts per pixel, and normalized to the cerebellum. Activity in the frontal, temporal and parieto-occipital cortices, and the thalami and basal ganglia, were compared between the two scans. Correlations between activity in each region of interest and Ham-D values were also determined. There were marked decreases in rCBF in the temporal lobes on the premenstrual scan compared to the postmenstrual scan in PMS patients. Significant correlations were observed between the change in rCBF in the right and left temporal lobes and the changes in Ham-D scores (r = 0.91, p < 0.01 and r = 0.86, p = 0.01 respectively). No rCBF changes were observed in controls. We conclude that SPECT imaging demonstrates modest decreases in rCBF in the temporal lobes that correlate with the level of depression in subjects with PMS.