Grey matter hypometabolism and atrophy in Parkinson's disease with cognitive impairment: a two-step process.

The pathophysiological process underlying cognitive decline in Parkinson's disease is not well understood. Cerebral atrophy and hypometabolism have been described in patients with Parkinson's disease and dementia or mild cognitive impairment with respect to control subjects. However, the exact relationships between atrophy and hypometabolism are still unclear. To determine the extension and topographical distribution of hypometabolism and atrophy in the different cognitive states of Parkinson's disease, we examined 46 patients with Parkinson's disease (19 female, 27 male; 71.7 ± 5.9 years old; 14.6 ± 4.2 years of disease evolution; modified Hoehn and Yahr mean stage 3.1 ± 0.7). Cognitive status was diagnosed as normal in 14 patients, as mild cognitive impairment in 17 and as dementia in 15 patients. Nineteen normal subjects (eight female, 11 male; 68.1 ± 3.2 years old) were included as controls. (18)F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging scans were obtained, co-registered, corrected for partial volume effect and spatially normalized to the Montreal Neurological Institute space in each subject. Smoothing was applied to the positron emission tomography and magnetic resonance imaging scans to equalize their effective smoothness and resolution (10 mm and 12 mm full-width at half-maximum and Gaussian kernel, respectively). Z-score maps for atrophy and for hypometabolism were obtained by comparing individual images to the data set of control subjects. For each group of patients, a paired Student's t-test was performed to statistically compare the two Z-map modalities (P < 0.05 false discovery rate corrected) using the direct voxel-based comparison technique. In patients with mild cognitive impairment, hypometabolism exceeded atrophy in the angular gyrus, occipital, orbital and anterior frontal lobes. In patients with dementia, the hypometabolic areas observed in the group with mild cognitive impairment were replaced by areas of atrophy, which were surrounded by extensive zones of hypometabolism. Areas where atrophy was more extended than hypometabolism were found in the precentral and supplementary motor areas in both patients with mild cognitive impairment and with dementia, and in the hippocampus and temporal lobe in patients with dementia. These findings suggest that there is a gradient of severity in cortical changes associated with the development of cognitive impairment in Parkinson's disease in which hypometabolism and atrophy represent consecutive stages of the same process in most of the cortical regions affected.

Systolic prospectively ECG-triggered dual-source CT angiography for evaluation of the coronary arteries in heart transplant recipients.

OBJECTIVES: To assess feasibility, image quality, and radiation dose of prospectively ECG-triggered coronary CT angiography (CTA) in orthotopic heart transplant (OHT) recipients. METHODS: 47 consecutive OHT recipients (40 men, mean age 62.1 ± 10.9 years, mean heart rate 86.3 ± 14.4 bpm) underwent dual-source CTA to rule out coronary allograft vasculopathy in a prospectively ECG-triggered mode with data acquisition during 35% to 45% of the cardiac cycle. Two independent observers blindly assessed image quality on a per-segment and per-vessel basis using a four-point scale (1-excellent, 4-not evaluable). Scores 1-3 were considered acceptable for diagnosis. Multivariate analysis was performed to evaluate differences between image quality scores obtained at different reconstruction intervals. Effective radiation doses were calculated. RESULTS: 671 coronary segments were evaluated. Interobserver agreement on the image quality was κ=0.75. Diagnostic image quality was observed in 93.9%, 95.5% and 93.3% of the segments at 35%, 40% and 45% reconstruction intervals. Mean image quality score was 1.5 ± 0.7 for the entire coronary tree, 1.4 ± 0.7 for the RCA, 1.6 ± 0.8 for the LCA and 1.6 ± 0.7 for the Cx at the best reconstruction interval. Estimated mean radiation dose was 4.5 ± 1.2 mSv. CONCLUSION: Systolic prospectively ECG-triggered CTA allows diagnostic image quality coronary angiograms in OHT recipients at low radiation doses.

Progression of dopaminergic depletion in a model of MPTP-induced Parkinsonism in non-human primates. An (18)F-DOPA and (11)C-DTBZ PET study.

UNLABELLED: Dopaminergic depletion in the nigrostriatal system is the neurochemical hallmark of Parkinson's disease (PD). Although numerous efforts have been made to determine the evolution of dopaminergic depletion in PD, "in vivo" data concerning the stages of this process are still scarce. We evaluated 6-[18F]-fluoro-l-DOPA ((18)F-DOPA) and 11C-(+)-alpha-dihydrotetrabenazine ((11)C-DTBZ) using PET in a model of chronically MPTP-induced parkinsonism in non-human primates. METHODS: Sixty-seven cynomolgus monkeys (Macacafascicularis) were included in the study. Progressive parkinsonism was induced by repeated administration of small doses of MPTP (iv) over several months. Animals were classified as controls, asymptomatic, recovered (having exhibited parkinsonian features transiently) and stable parkinsonian, according to their motor status. Analysis of striatal dopaminergic activity was conducted by regions of interest (ROI) and statistical parametric mapping (SPM) over normalized parametric images. RESULTS: A progressive loss of striatal uptake was evident among groups for both radiotracers, which correlated significantly with the clinical motor status. Changes occurred earlier, i.e. in the less affected stages, with (11)C-DTBZ. Similar results were achieved by ROI and SPM analysis. Uptake was similar with both radiotracers for the asymptomatic and recovered groups. CONCLUSIONS: Serial assessment with (18)F-DOPA and (11)C-DTBZ PETs provides an effective approach to evaluate evolution of dopaminergic depletion in monkeys with MPTP-induced parkinsonism. This approach could be useful to perform studies aiming to test the effect of early therapeutic intervention and putative neuroprotective treatments.

Coupling of cerebral blood flow and functional connectivity is decreased in healthy aging.

Aging leads to cerebral perfusion and functional connectivity changes that have been assessed using various neuroimaging techniques. In addition, a link between these two parameters has been demonstrated in healthy young adults. In this work, we employed arterial spin labeling (ASL) fMRI to measure global and voxel-wise differences in cerebral blood flow (CBF) and intrinsic connectivity contrast (ICC) in the resting state in a group of cognitively normal elderly subjects and a group of cognitively normal young subjects, in order to assess the effects of aging on CBF-ICC coupling, which had not been previously evaluated. Our results showed age-related global and regional CBF decreases in prefrontal mesial areas, lateral frontal regions, insular cortex, lateral parietal areas, precuneus and occipital regions. Subcortically, perfusion was reduced in the medial thalamus and caudate nucleus. ICC was also found reduced with age in prefrontal cortical areas and insular cortex, affecting key nodes of the default mode and salience networks. Areas of ICC and CBF decrease partially overlapped, however, the CBF reduction was more extensive and encompassed more areas. This dissociation was accompanied by a decrease in CBF-ICC coupling. These results suggest that aging leads to a disruption in the relationship between CBF and intrinsic functional connectivity that could be due to neurovascular dysregulation.

Reduced Cerebral Blood Flow in Mild Cognitive Impairment Assessed Using Phase-Contrast MRI.

There is increasing evidence of a vascular contribution to Alzheimer's disease (AD). In some cases, prior work suggests that chronic brain hypoperfusion could play a prime pathogenic role contributing to the accumulation of amyloid-ß,while other studies favor the hypothesis that vascular dysfunction and amyloid pathology are independent, although synergistic, mechanisms contributing to cognitive impairment. Vascular dysfunction can be evaluated by assessing cerebral blood flow impairment. Phase contrast velocity mapping by MRI offers a non-invasive means of quantifying the total inflow of blood to the brain. This quantitative parameter could be a sensitive indicator of vascular disease at early stages of AD. In this work, phase contrast MRI was used to evaluate cerebral hemodynamics in patients with subjective memory complaints, amnestic mild cognitive impairment, and mild to moderate AD, and compare them with control subjects. Results showed that blood flow and velocity were decreased in the patients with cognitive dysfunction and the decrease correlated with the degree of cognitive impairment as assessed by means of neuropsychological tests. Total cerebral blood flow measurements were clearly reduced in AD patients, but more importantly appeared to be sensitive enough to distinguish between healthy subjects and those with mild cognitive impairment. A quantitative measurement of total brain blood flow could potentially predict vascular dysfunction and compromised brain perfusion in early stages of AD.

Neuroimaging as a marker of the onset and progression of Alzheimer's disease.

Several neuroimaging techniques are promising tools as early markers of brain pathology in Alzheimer's disease (AD). On structural MRI, atrophy of the entorhinal cortex is present already in mild cognitive impairment (MCI). In the autosomal dominant forms of AD, the rate of atrophy of medial temporal structures separates affected from control persons even 3 years before the clinical onset of cognitive impairment. The elevated annual rate of brain atrophy offers a surrogate tool for the evaluation of newer therapies using smaller samples, thereby saving time and resources. On functional MRI, activation paradigms activate a larger area of parieto-temporal association cortex in persons at higher risk for AD, whereas the entorhinal cortex activation is lesser in MCI. Similar findings have been detected with activation procedures and water (H(2)(15)O) PET. Regional metabolism in the entorhinal cortex, studied with FDG PET, seems to predict normal elderly who will deteriorate to MCI or AD. SPECT shows decreased regional perfusion in limbic areas, both in MCI and AD, but with a lower likelihood ratio than PET. Newer PET compounds allow for the determination in AD of microglial activation, regional deposition of amyloid and the evaluation of enzymatic activity in the brain of AD patients.

Functional bold MRI: advantages of the 3 T vs. the 1.5 T.

We quantitatively evaluate the benefits of a higher field strength for functional brain MRI (fMRI) based on the blood oxygenation level-dependent contrast. The 3-T fMRI shows a higher sensitivity for the motor and somatosensory stimulation and more specific localization in the grey substance. The 3-T fMRI detects additional areas of activation with the motor paradigm.

Preoperative planning of DIEP and SGAP flaps: preliminary experience with magnetic resonance angiography using 3-tesla equipment and blood-pool contrast medium.

BACKGROUND: Autologous breast reconstruction techniques can be used to create a breast, in particular the superior gluteal artery perforator (SGAP) and deep inferior epigastric artery perforator (DIEP) flaps. Preoperative imaging is an essential planning tool in mapping the location and size of perforator vessels. The aim of this report is to show the usefulness of angio-MR technique for preoperative planning of DIEP and SGAP flaps. Initial experience, surgical findings correlation and imaging findings will be described. METHODS: From February 2007 to September 2007, ten consecutive women considered for breast reconstruction with DIEP (eight patients) and SGAP flaps (two patients) after previous mastectomy for breast cancer were studied. After written informed consent was obtained, a preoperative angio-MR using 3-Tesla equipment and blood-pool contrast medium was performed to localize and evaluate the main perforator vessels in each patient and procedure. RESULTS: Angio-MR showed all the main perforator vessels later observed during the surgical procedure with a very good location concordance, but missed one main perforator vessels in each of two patients. In all patients undergoing SGAP flaps, an accurate identification of the main perforator vessels was achieved. Angio-MR clearly showed the intramuscular course of the perforator vessels for DIEP and SGAP flaps. Exact correlation between angio-MR and surgical findings was observed. CONCLUSIONS: The use of angio-MR for preoperative perforator flaps evaluation yielded promising results and would allow not only to locate perforator vessels but also to globally assess presurgical planning of perforator flaps in a noninvasive, radiation and toxicity-free way.

Adenosine-stress dynamic myocardial volume perfusion imaging with second generation dual-source computed tomography: Concepts and first experiences.

Recent research suggests that multidetector-row CT may have potential as a standalone modality for integrative imaging of coronary heart disease, including the assessment of the myocardial blood supply. However, the technical prerequisites for volumetric, time-resolved imaging of the passage of a contrast medium bolus through the myocardium have only been met with latest generation wide-detector CT scanners. Second-generation dual-source CT enables performing electrocardiographic (ECG)-synchronized dynamic myocardial perfusion imaging by a dedicated "shuttle" mode. With this acquisition mode, image data can be acquired during contrast medium infusion at 2 alternating table positions with the table shuttling back and forth between the 2 positions covering a 73-mm anatomic volume. We applied this acquisition technique for detecting differences in perfusion patterns between healthy and diseased myocardium and for quantifying myocardial blood flow under adenosine stress in 3 patients with coronary heart disease. According to our initial experience, the addition of adenosine stress volumetric dynamic CT perfusion to a cardiac CT protocol comprising coronary artery calcium quantification, prospectively ECG-triggered coronary CT angiography, and delayed acquisition appears promising for the comprehensive assessment of coronary artery luminal integrity, cardiac function, perfusion, and viability with a single modality.

CT scan study of atlantoaxial rotatory mobility in asymptomatic adult subjects: a basis for better understanding C1-C2 rotatory fixation and subluxation.

STUDY DESIGN: Normal rotation was evaluated in a group of 40 asymptomatic adults. OBJECTIVE: To determine the normal rotational limits of C1-C2 in adults and define when a rotatory fixation occurs in the limits of normality or in subluxation. The term subluxation should be used only when C1-C2 is rotated beyond normal limits. SUMMARY OF BACKGROUND DATA: Concepts about rotatory fixation were established by accepting that it may occur within the limits of normal range of motion. Although nowadays CT is the current image method used to evaluate any case of torticollis, no study has been performed in adult population on what really normal rotation look like in CT scans. METHODS: The study included the measurement of the rotational movement of the neck and a CT scan study of the articular processes of C1-C2 in maximal, left and right, active rotation. A superposition of 6 consecutive slices was carried out, obtaining a linear contour of the axial view of C1-C2. Rotation angle and contact surface loss were measured. RESULTS: The average neck rotation angle was 79 degrees (range: 74 degrees to 81 degrees ). The superposition of the images taken in every rotational direction showed a wide contact loss between the correspondent C1-C2 articular surfaces (42.4%-85.7%; average: 70%). The report of these images, carried out by 3 independent radiologists, concluded that there was a rotatory subluxation in all these cases. CONCLUSION: Our results coincide with our previous published ones conducted in children, and lead us to conclude that a CT scan showing wide-but incomplete-rotational facet displacement is not sufficient to define subluxation. We perceive that there is a risk of overdiagnosis and overtreatment (C1-C2 arthrodesis) when evaluating upper cervical spine rotational problems. The concept of both rotatory fixation and subluxation should be revised, and quantifying the rotational angle and contact surface loss between C1-C2 can be very useful.

Independent association of fibrinogen with carotid intima-media thickness in asymptomatic subjects.

BACKGROUND: Fibrinogen has been found to be an independent risk factor for cardiovascular disease. Both genetic and environmental factors contribute to its variability in plasma. However, whether the relation between fibrinogen and carotid intima-media thickness (IMT) is independent of those factors has not been established. Therefore, the aim of this study was to investigate the relations of plasma fibrinogens and the -455 G/A Bbeta-fibrinogen polymorphism with the carotid IMT in a series of asymptomatic subjects. METHODS: Markers of inflammation, C-reactive protein (CRP) and leukocytes, and endothelial perturbation (von Willebrand factor, vWF) were measured in 135 subjects. All individuals underwent a complete clinical examination and lipid measurements (cholesterol and its fractions HDL and LDL and triglycerides). The carotid IMT was measured by B-mode ultrasound in the common carotid artery. RESULTS: Patients in the highest fibrinogen tertile had a significantly higher BMI (p < 0.01), LDL-cholesterol (p < 0.01), leukocyte count, CRP and vWF (p < 0.001). In the univariate model a strong positive relationship was found between plasma fibrinogen and carotid IMT (p < 0.01). Fibrinogen also correlated positively with age, BMI, arterial systolic pressure, cholesterol, cholesterol-LDL, smoking, CRP and vWF (p < 0.01). In the multivariate analysis, the association of fibrinogen with carotid IMT remained significant (p < 0.01) after adjustment for all the parameters analyzed. CONCLUSION: In a population sample of adults without clinically overt atherosclerotic disease, elevated fibrinogen was related to carotid IMT independent of a wide range of important confounding variables.