The neural correlates of perceived energy levels in older adults with late-life depression.

Late-life depression is common among older adults. Although white-matter abnormality is highly implicated, the extent to which the corticospinal tract is associated with the pathophysiology of late-life depression is unclear. The current study aims to investigate the white-matter structural integrity of the corticospinal tract and determine its cognitive and functional correlates in older adults with late-life depression. Twenty-eight older adults with clinical depression and 23 healthy age-matched older adults participated in the study. The white matter volume and the white matter hyperintensities (WMHs) of the corticospinal tract, as well as the global WMHs, were measured. Psychomotor processing speed, severity of depression, perceived levels of energy and physical functioning were measured to examine the relationships among the correlates in the depressed participants. The right corticospinal tract volume was significantly higher in depressed older adults relative to healthy controls. Moreover, the right corticospinal tract volume was significantly associated with the overall severity of depression and accounted for 17% of its variance. It further attenuated the relationship between the severity of depression and perceived levels of energy. Our findings suggested that higher volume in the right corticospinal tract is implicated in LLD and may relate to lower perceived levels of energy experienced by older adults with depression.

Association Between Flow Acceleration in the Carotid Artery and Intracranial Aneurysms.

OBJECTIVES: In physiologic pulsatile flow, velocity acceleration is an independent factor determining wall shear stress experienced by the vascular endothelium. The purpose of this study was to evaluate Doppler indices of systolic velocity acceleration in extracranial cerebral vessels and the occurrence of intracranial aneurysms. METHODS: We reviewed medical records and 3.0-T brain magnetic resonance imaging with 3-dimensional time-of-flight magnetic resonance angiography of 1323 adults who underwent health checkups from June 2006 to November 2011, in whom 53 intracranial aneurysms were identified in 45 patients. Doppler ultrasound parameters of the carotid and vertebral arteries were analyzed in these 45 patients with aneurysms and compared with another 45 control participants matched for age and sex. We defined the maximum systolic acceleration (ACCmax ) as the maximum slope of the early phase of systolic acceleration on the Doppler waveform and the maximum acceleration index (AImax ) as the ratio of the ACCmax and peak systolic velocity. RESULTS: The Doppler analysis showed a significantly increased AImax and ACCmax in the common carotid artery (CCA), internal carotid artery, and vertebral artery in the aneurysm group. A cutoff 13.89 s-1 for the AImax of the CCA had sensitivity of 80% with a negative predictive value of 99% for intracranial aneurysms. CONCLUSIONS: This study suggests that the AImax of the CCA with a cutoff of 13.89 s-1 may be an alternative to 3-dimensional time-of-flight magnetic resonance angiography or computed tomographic angiography as a screening tool for intracranial aneurysms. Further prospective studies are needed to validate the diagnostic performance and cost-effectiveness of these indices for screening.

The relationships between brain structural changes and perceived loneliness in older adults suffering from late-life depression.

OBJECTIVE: Late-life depression is a significant health risk factor for older adults, part of which is perceived loneliness. In this voxel-based morphometry study, we examined the relationships between perceived loneliness and depression recurrence. METHODS: Fifty-two older adults were recruited, and they were split into 3 groups: single episode, multiple episodes, or normal control groups, according to their clinical histories. RESULTS: This result suggests the level of functioning regarding the reward system may be negatively related to the number of depressive episodes. Taken together, the findings of this study offer important insight into the neural underpinnings of the course and chronicity of late-life depression.

Dual-phase 18F-florbetapir positron emission tomography in patients with primary progressive aphasia, Alzheimer's disease, and healthy controls: A preliminary study.

BACKGROUND/PURPOSE: To determine whether dual-phase 18F-florbetapir positron emission tomography imaging with perfusion-like and amyloid deposition information can distinguish among primary progressive aphasia (PPA), Alzheimer's disease (AD), and healthy controls (HCs). METHODS: Patients diagnosed with PPA, including four semantic dementia (SD) and two progressive nonfluent aphasia (PNFA), as well as one logopenic variant (LV) of PPA, were studied. All PPA patients, and age-/sex-matched patients with probable AD (n=8) and HCs (n=8) were subjected to dual-phase 18F-florbetapir imaging. Atlas-based quantitative volumes of interest (VOIs) analysis for six cortical areas and whole cerebellum was performed. The standardized uptake value ratios were calculated by normalizing the dual-phase-integrated activities of the six VOIs to whole cerebellum counts. RESULTS: Early phase 18F-florbetapir image showed significantly lower global perfusion index in six PPA patients as compared with HCs. According to VOI analysis, the hypoperfusion lesions were identified in the frontal, anterior cingulate, parietal, precuneus, and temporal regions. Similar findings were confirmed by voxel-base image comparison. 18F-florbetapir late-phase image showed significantly increased amyloid burden in the global cortex index and all six brain regions of eight AD and LV patients when compared with the other six PPA patients and eight HCs. There was no apparent uptake of amyloid tracer in both six PPA patients and eight HCs. CONCLUSION: Dual-phase 18F-florbetapir images of six PPA (SD and PNFA) patients showed hypoperfusion in the frontotemporal cortex, and little global amyloid uptake, which may be a distinct image pattern for differentiation among HC, AD, and PPA patients.

Digit symbol substitution test score and hyperhomocysteinemia in older adults.

Mounting evidence shows that hyperhomocysteinemia is a risk factor for cognitive decline. This study enrolled subjects with normal serum levels of B12 and folate and performed thorough neuropsychological assessments to illuminate the independent role of homocysteine on cognitive functions.Participants between ages 50 and 85 were enrolled with Modified Hachinski ischemic score of <4, adequate visual and auditory acuity to allow neuropsychological testing, and good general health. Subjects with cognitive impairment resulting from secondary causes were excluded. Each of the participants completed evaluations of general intellectual function, including the Mini-Mental State Examination, Cognitive Abilities Screening Instrument, Clinical Dementia Rating, and a battery of neuropsychological assessments.This study enrolled 225 subjects (90 subjects younger than 65 years and 135 subjects aged 65 years or older). The sex proportion was similar between the 2 age groups. Years of education were significantly fewer in the elderly (7.49 ±â€Š5.40 years) than in the young (9.76 ±â€Š4.39 years, P = 0.001). There was no significant difference in body mass index or levels of vitamin B12 and folate between the 2 age groups. Homocysteine levels were significantly higher in the elderly group compared to the younger group (10.8 ±â€Š2.7 vs. 9.5 ±â€Š2.5 µmol/L, respectively, P = 0.0006). After adjusting for age, sex, and education, only the Digit Symbol Substitution (DSS) score was significantly lower in subjects with hyperhomocysteinemia (homocysteine >12 µmol/L) than those with homocysteine ≤12 µmol/L in the elderly group (DSS score: 7.1 ±â€Š2.7 and 9.0 ±â€Š3.0, respectively, beta = -1.6, 95% confidence interval [CI] = -2.8∼-0.5, P = 0.001) and borderline significance was noted in the combined age group (beta = -1.1, 95% CI = -2.1∼-0.1, P = 0.04). We did not find an association between hyperhomocysteinemia and other neuropsychological assessments.This is the first study to demonstrate a significant association between hyperhomocysteinemia (>12 µmol/L) and low DSS score, suggesting that DSS score may be an independent marker of cognitive impairment in response to hyperhomocysteinemia, especially in the elderly. Further replication studies with larger cohorts are needed to confirm our results.

Neural correlates of motor recovery after robot-assisted stroke rehabilitation: a case series study.

Robot-assisted bilateral arm therapy (RBAT) has shown promising results in stroke rehabilitation; however, connectivity mapping of the sensorimotor networks after RBAT remains unclear. We used fMRI before and after RBAT and a dose-matched control intervention (DMCI) to explore the connectivity changes in 6 subacute stroke patients. Sensorimotor functions improved in the RBAT and DMCI groups after treatment. Enhanced activation changes were observed in bilateral primary motor cortex (M1) and bilateral supplementary motor area (SMA) after RBAT. Dynamic causal model analysis revealed that interhemispheric connections were enhanced in RBAT patients. These preliminary findings suggest that intracortical and intercortical coupling might underlie poststroke RBAT.

Alterations of diffusion tensor MRI parameters in the brains of patients with Parkinson's disease compared with normal brains: possible diagnostic use.

OBJECTIVES: To investigate the diagnostic performance of diffusion tensor imaging in patients with Parkinson's disease (PD). METHODS: We examined a total of 126 PD patients (68 males/58 females, mean age: 62.0 ±7.6 years) and 91 healthy controls (43 males/48 females, mean age: 59.8 ±7.2 years). Images were acquired on a 3 Tesla magnetic resonance scanner. The Camino software was used to normalize and parcellate diffusion-weighted images into 90 cerebral regions based on the automatic anatomical labelling template. The minimum, median, and maximum values of the mean/radial/axial diffusivity/fractional anisotropy were determined. The diagnostic performance was assessed by receiver operating characteristic analysis. The associations of imaging parameters with disease severity were tested using Pearson's correlation coefficients after adjustment for disease duration. RESULTS: Compared with healthy controls, PD patients showed increased diffusivity in multiple cortical regions that extended beyond the basal ganglia. An area under curve of 85 % was identified for the maximum values of mean diffusivity in the ipsilateral middle temporal gyrus. The most significant intergroup difference was 26.8 % for the ipsilateral inferior parietal gyrus. CONCLUSION: The measurement of water diffusion from the parcellated cortex may be clinically useful for the assessment of PD patients. KEY POINTS: • Increased diffusivity was identified in multiple cortical regions of Parkinson's disease patients. • The area under the receiver operating curve was 85 % in the middle temporal gyrus. • The ipsilateral inferior parietal gyrus showed the most significant change.

Neuroplastic changes in resting-state functional connectivity after stroke rehabilitation.

Most neuroimaging research in stroke rehabilitation mainly focuses on the neural mechanisms underlying the natural history of post-stroke recovery. However, connectivity mapping from resting-state fMRI is well suited for different neurological conditions and provides a promising method to explore plastic changes for treatment-induced recovery from stroke. We examined the changes in resting-state functional connectivity (RS-FC) of the ipsilesional primary motor cortex (M1) in 10 post-acute stroke patients before and immediately after 4 weeks of robot-assisted bilateral arm therapy (RBAT). Motor performance, functional use of the affected arm, and daily function improved in all participants. Reduced interhemispheric RS-FC between the ipsilesional and contralesional M1 (M1-M1) and the contralesional-lateralized connections were noted before treatment. In contrast, greater M1-M1 functional connectivity and disturbed resting-state networks were observed after RBAT relative to pre-treatment. Increased changes in M1-M1 RS-FC after RBAT were coupled with better motor and functional improvements. Mediation analysis showed the pre-to-post difference in M1-M1 RS-FC was a significant mediator for the relationship between motor and functional recovery. These results show neuroplastic changes and functional recoveries induced by RBAT in post-acute stroke survivors and suggest that interhemispheric functional connectivity in the motor cortex may be a neurobiological marker for recovery after stroke rehabilitation.

Human amygdala activation by the sound produced during dental treatment: A fMRI study.

During dental treatments, patients may experience negative emotions associated with the procedure. This study was conducted with the aim of using functional magnetic resonance imaging (fMRI) to visualize cerebral cortical stimulation among dental patients in response to auditory stimuli produced by ultrasonic scaling and power suction equipment. Subjects (n = 7) aged 23-35 years were recruited for this study. All were right-handed and underwent clinical pure-tone audiometry testing to reveal a normal hearing threshold below 20 dB hearing level (HL). As part of the study, subjects initially underwent a dental calculus removal treatment. During the treatment, subjects were exposed to ultrasonic auditory stimuli originating from the scaling handpiece and salivary suction instruments. After dental treatment, subjects were imaged with fMRI while being exposed to recordings of the noise from the same dental instrument so that cerebral cortical stimulation in response to aversive auditory stimulation could be observed. The independent sample confirmatory t-test was used. Subjects also showed stimulation in the amygdala and prefrontal cortex, indicating that the ultrasonic auditory stimuli elicited an unpleasant response in the subjects. Patients experienced unpleasant sensations caused by contact stimuli in the treatment procedure. In addition, this study has demonstrated that aversive auditory stimuli such as sounds from the ultrasonic scaling handpiece also cause aversive emotions. This study was indicated by observed stimulation of the auditory cortex as well as the amygdala, indicating that noise from the ultrasonic scaling handpiece was perceived as an aversive auditory stimulus by the subjects. Subjects can experience unpleasant sensations caused by the sounds from the ultrasonic scaling handpiece based on their auditory stimuli.

A simple method to improve the quality of diffusion-weighted magnetic resonance imaging with rapid histologic correlation in a murine model.

Diffusion-weighted magnetic resonance imaging (DW-MRI) has been used extensively in biomedical research. However, this technique has often suffered from distortion artifacts because of the magnetic field inhomogeneity surrounding the tissues. Histology is important for validating MRI interpretations, but correlating MRIs with tissue samples is challenging. Here we propose a method to improve DW-MRI and facilitate the matching between MRIs and tissue samples. A cryostat embedding medium, optimal cutting temperature (OCT) compound, was used to cover the examined target during the MRI studies. Frozen OCT compound could aid the examined target to be sectioned in parallel with the imaging plane. Phantom experiments demonstrated that embedding in OCT compound improved the magnetic field inhomogeneity while maintaining the apparent diffusion coefficient. Animal experiments revealed significantly reduced distortions in DW images in both the axial and coronal planes. The in vivo MRIs were easily matched with histologic specimens in a slice-to-slice fashion to examine the corresponding tissue microenvironment. This simple method might improve the quality of DW-MRI and provide histologic information for MRI to serve as an image biomarker.

Tract-based spatial statistics: application to mild cognitive impairment.

RATIONALE AND OBJECTIVES: The primary objective of the current investigation was to characterize white matter integrity in different subtypes of mild cognitive impairment (MCI) using tract-based spatial statistics of diffusion tensor imaging. MATERIALS AND METHODS: The study participants were divided into 4 groups of 30 subjects each as follows: cognitively healthy controls, amnestic MCI, dysexecutive MCI, and Alzheimer's disease (AD). All subjects underwent a comprehensive neuropsychological assessment, apolipoprotein E genotyping, and 3-tesla MRI. The diffusion tensor was reconstructed and then analyzed using tract-based spatial statistics. The changes in brain white matter tracts were also examined according to the apolipoprotein E ε 4 status. RESULTS: Compared with controls, amnestic MCI patients showed significant differences in the cerebral white matter, where changes were consistently detectable in the frontal and parietal lobes. We found a moderate impact of the apolipoprotein E ε 4 status on the extent of white matter disruption in the amnestic MCI group. Patients with AD exhibited similar but more extensive alterations, while no significant changes were observed in dysexecutive MCI patients. CONCLUSION: The results from this study indicate that amnestic MCI is the most likely precursor to AD as both conditions share significant white matter damage. By contrast, dysexecutive MCI seems to be characterized by a distinct pathogenesis.

Magnetic-resonance imaging for kinetic analysis of permeability changes during focused ultrasound-induced blood-brain barrier opening and brain drug delivery.

Focused ultrasound (FUS) with the presence of microbubbles has been shown to induce transient and local opening of the blood-brain barrier (BBB) for the delivery of therapeutic molecules which normally cannot penetrate into the brain. The success of FUS brain-drug delivery relies on its integration with in-vivo imaging to monitor kinetic change of therapeutic molecules into the brain. In this study, we developed a dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) technique for kinetic analysis of delivered molecules during FUS-BBB opening. Three kinetic parameters (Ktrans, Ve, Kep) were characterized dynamically to describe BBB-permeability at two FUS exposure conditions (0.4 or 0.8MPa) over 24h. Ktrans, defined as the influx volume transfer constant from plasma to EES, and Ve, the EES volume fraction, were both found to be pressure-dependent. Ktrans and Ve showed a peak increase of 0.0086-0.0131min(-1) (for 0.4-0.8MPa pressure), and 0.0431-0.0692, respectively, immediately after FUS exposure. Both parameters subsequently decreased exponentially as a function of time, with estimated half-lives of decay of 2.89-5.3 and 2.2-4.93h, respectively. The kinetics of Kep, defined as the efflux rate constant from the extracellular extravascular space (EES) to the plasma, were complementary to Ktrans, with an initial decrease from 0.2010 to 0.1901min(-1) followed by a significantly longer recovery time (half-life of 17.39-99.92h). Our observations strongly supported the existence of imbalanced and mismatched kinetics of influx (Ktrans) and efflux (Kep) between the plasma and EES, indicating the existence of directional permeability during FUS-BBB opening. We further showed that kinetic change determined by DCE-MRI correlated well with the concentration of Evans Blue (EB)-albumin (coefficient of 0.74-0.89). These findings suggest that MRI kinetic monitoring may serve as an alternative method for in-vivo monitoring of pharmacokinetics and pharmacodynamics (PK/PD) change of therapeutic agents during drug delivery to the brain, and provide useful information for future optimization of FUS-BBB opening.

Impact of coexisting coronary artery disease on the occurrence of cerebral ischemic lesions after carotid stenting.

BACKGROUND: Coronary artery disease (CAD) may coexist with extracranial carotid artery stenosis (ECAS), but the influence of CAD on procedure-related complications after carotid artery stenting (CAS) has not been well investigated. The study aimed to determine the impact of CAD on the occurrence of peri-CAS cerebral ischemic lesions on diffusion-weighted imaging (DWI) scanning. METHODS: Coronary angiography was performed within six months before CAS. DWI scanning was repetitively done within 1 week before and after CAS. Clinical outcome measures were stroke, angina, myocardial infarction and death within 30 days. RESULTS: Among 126 patients (69.5±9.0 years) recruited for unilateral protected CAS, 33 (26%) patients had peri-CAS DWI-positive lesions. CAD was noted in 79% (26 in 33) and 48% (45 in 93) of patients with and without peri-CAS DWI-positive lesions (OR, 4.0; 95% CI, 1.6-10.0; P = .0018), and the number of concomitant CAD on coronary angiography was positively correlated with the risk for peri-CAS DWI-positive lesions (P = .0032). In patients with no CAD (n = 55), asymptomatic CAD (n = 41) and symptomatic CAD (n = 30), the occurrence rates of peri-CAS DWI-positive lesions were 13%, 41% and 30% (P = .0048), and the peri-CAS stroke rates were 2%, 7% and 0% (P = .2120). CONCLUSIONS: The severity of morphological CAD and the presence of either symptomatic or asymptomatic CAD are associated with the occurrence of peri-CAS cerebral ischemic lesions.

Increased brain amyloid deposition in patients with a lifetime history of major depression: evidenced on 18F-florbetapir (AV-45/Amyvid) positron emission tomography.

PURPOSE: The literature suggests that a history of depression is associated with an increased risk of developing Alzheimer's disease (AD). The aim of this study was to examine brain amyloid accumulation in patients with lifetime major depression using (18)F-florbetapir (AV-45/Amyvid) PET imaging in comparison with that in nondepressed subjects. METHODS: The study groups comprised 25 depressed patients and 11 comparison subjects who did not meet the diagnostic criteria for AD or amnestic mild cognitive impairment. Vascular risk factors, homocysteine and apolipoprotein E (ApoE) genotype were also examined. The standard uptake value ratio (SUVR) of each volume of interest was analysed using whole the cerebellum as the reference region. RESULTS: Patients with a lifetime history of major depression had higher (18)F-florbetapir SUVRs in the precuneus (1.06 ± 0.08 vs. 1.00 ± 0.06, p = 0.045) and parietal region (1.05 ± 0.08 vs. 0.98 ± 0.07, p = 0.038) than the comparison subjects. Voxel-wise analysis revealed a significantly increased SUVR in depressed patients in the frontal, parietal, temporal and occipital areas (p < 0.01). There were no significant associations between global (18)F-florbetapir SUVRs and prior depression episodes, age at onset of depression, or time since onset of first depression. CONCLUSION: Increased (18)F-florbetapir binding values were found in patients with late-life major depression relative to comparison subjects in specific brain regions, despite no differences in age, sex, education, Mini Mental Status Examination score, vascular risk factor score, homocysteine and ApoE ε4 genotype between the two groups. A longitudinal follow-up study with a large sample size would be worthwhile.

Sex dimorphism of cortical water diffusion in normal aging measured by magnetic resonance imaging.

BACKGROUND: The purpose of this study was to examine sex dimorphism in water diffusion in the brain throughout the normal aging process by magnetic resonance imaging. METHODS: Diffusion-weighted images covering the majority of the brain were acquired from 77 healthy participants. Both the mean water diffusivity and diffusion kurtosis were calculated from the cortical regions and parcellated according to the template in anatomical automatic labeling. The mean water diffusivity and diffusion kurtosis from both sexes were examined and subsequently correlated with age. Statistical significance was set at a threshold of p < 0.01 after correction for multiple comparisons. In regions that reached statistical significance, a linear regression model was performed. Analysis of variance was conducted to determine the interaction between aging and sex. RESULTS: Sex differences were observed for three aspects. First, compared to females, males presented increased mean water diffusivity and a decreased diffusion kurtosis in the frontal and temporal lobes. Second, a widespread age-related increase in mean water diffusivity was observed, which was more significant in the frontal, occipital, and temporal areas and in the cingulum in females. Third, the diffusion kurtosis decreased with aging but only in restricted areas for both sexes. For the interaction of aging and sex, the most significant change was observed with regards to mean diffusivity, mostly in the right amygdala. CONCLUSIONS: A sex-related dimorphism in water diffusion throughout the aging process was observed in the cortex using magnetic resonance imaging.

Discrimination between Alzheimer's disease and mild cognitive impairment using SOM and PSO-SVM.

In this study, an MRI-based classification framework was proposed to distinguish the patients with AD and MCI from normal participants by using multiple features and different classifiers. First, we extracted features (volume and shape) from MRI data by using a series of image processing steps. Subsequently, we applied principal component analysis (PCA) to convert a set of features of possibly correlated variables into a smaller set of values of linearly uncorrelated variables, decreasing the dimensions of feature space. Finally, we developed a novel data mining framework in combination with support vector machine (SVM) and particle swarm optimization (PSO) for the AD/MCI classification. In order to compare the hybrid method with traditional classifier, two kinds of classifiers, that is, SVM and a self-organizing map (SOM), were trained for patient classification. With the proposed framework, the classification accuracy is improved up to 82.35% and 77.78% in patients with AD and MCI. The result achieved up to 94.12% and 88.89% in AD and MCI by combining the volumetric features and shape features and using PCA. The present results suggest that novel multivariate methods of pattern matching reach a clinically relevant accuracy for the a priori prediction of the progression from MCI to AD.

A comparison of benign and inflammatory manifestations of Tolosa-Hunt syndrome.

BACKGROUND: Tolosa-Hunt syndrome (THS) manifests as a benign or an inflammatory type disease. The nosography differences between these types remain to be elucidated. We aimed to analyze and compare the clinical presentations of benign and inflammatory THS. METHODS: The ward patients who presented with THS from January 1990 to May 2011 were retrospectively reviewed. THS was diagnosed according to the recommendations of the International Headache Society. RESULTS: Of the 53 THS cases (49 patients), 30 (56.6%) were classified as benign and 23 (43.4%) as inflammatory THS. There were strong similarities between the groups in terms of clinical manifestations, laboratory findings, responses to glucocorticoid treatment, and outcomes. However, patients with inflammatory THS tended to be younger (mean age, 43.4 years; P 0.05) and have optic nerve dysfunction (56.5%; P 0.05) and longer disease duration (2.3 ± 1.0 months; P 0.05) compared to those with benign THS (mean age, 56.4 years; mean disease duration, 1.6 ± 0.7 months). The patients with additional involvement of both the optic nerve and the second division of the trigeminal nerve experienced a longer disease duration ( P 0.05). Additionally, patients with orbital pseudotumors had diplopia that responded poorly to treatment with glucocorticoids ( P 0.05). High-dose (>0.5 mg/kg/day) and low-dose (≤0.5 mg/kg/day) prednisolone were equally effective in relieving symptoms in both groups ( P > 0.05). CONCLUSION: Benign and inflammatory THS were highly similar in terms of nosography. The responses to glucocorticoid treatment were generally good except in patients with orbital pseudotumors.

Regional amyloid deposition in amnestic mild cognitive impairment and Alzheimer's disease evaluated by [18F]AV-45 positron emission tomography in Chinese population.

BACKGROUND: To compare the neocortical amyloid loads among cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and Alzheimer's disease (AD) subjects with [(18)F]AV-45 positron emission tomography (PET). MATERIALS AND METHODS: [(18)F]AV-45 PET was performed in 11 CN, 13 aMCI, and 12 AD subjects to compare the cerebral cortex-to-whole cerebellum standard uptake value ratios (SUVRs) of global and individual volumes of interest (VOIs) cerebral cortex. The correlation between global cortical [(18)F]AV-45 SUVRs and Mini-Mental State Examination (MMSE) scores was analyzed. RESULTS: The global cortical [(18)F]AV-45 SUVRs were significantly different among the CN (1.08±0.08), aMCI (1.27±0.06), and AD groups (1.34±0.13) (p = 0.0003) with amyloidosis positivity rates of 9%, 62%, and 92% in the three groups respectively. Compared to CN subjects, AD subjects had higher SUVRs in the global cortical, precuneus, frontal, parietal, occipital, temporal, and posterior cingulate areas; while aMCI subjects had higher values in the global cortical, precuneus, frontal, occipital and posterior cingulate areas. There were negative correlations of MMSE scores with SUVRs in the global cortical, precuneus, frontal, parietal, occipital, temporal, posterior cingulate and anterior cingulate areas on a combined subject pool of the three groups after age and education attainment adjustment. CONCLUSIONS: Amyloid deposition occurs relatively early in precuneus, frontal and posterior cingulate in aMCI subjects. Higher [(18)F]AV-45 accumulation is present in parietal, occipital and temporal gyri in AD subjects compared to the aMCI group. Significant correlation between MMSE scores and [(18)F]AV-45 SUVRs can be observed among CN, aMCI and AD subjects.

Noninvasive monitoring of microvascular changes with partial irradiation using dynamic contrast-enhanced and blood oxygen level-dependent magnetic resonance imaging.

PURPOSE: The microvasculature of a tumor plays an important role in its response to radiation therapy. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) and blood oxygen level-dependent (BOLD) MRI are both sensitive to vascular characteristics. The present study proposed a partial irradiation approach to a xenograft tumor to investigate the intratumoral response to radiation therapy using DCE and BOLD MRI. METHODS AND MATERIALS: TRAMP-C1 tumors were grown in C57BL/6J mice. Partial irradiation was performed on the distal half of the tumor with a single dose of 15 Gy. DCE MRI was performed to derive the endothelium transfer constant, K(trans), using pharmacokinetic analysis. BOLD MRI was performed using quantitative R2 measurements with carbogen breathing. The histology of the tumor was analyzed using hematoxylin and eosin staining and CD31 staining to detect endothelial cells. The differences between the irradiated and nonirradiated regions of the tumor were assessed using K(trans) values, ΔR2 values in response to carbogen and microvascular density (MVD) measurements. RESULTS: A significantly increased K(trans) and reduced BOLD response to carbogen were found in the irradiated region of the tumor compared with the nonirradiated region (P<.05). Histologic analysis showed a significant aggregation of giant cells and a reduced MVD in the irradiated region of the tumor. The radiation-induced difference in the BOLD response was associated with differences in MVD and K(trans). CONCLUSIONS: We demonstrated that DCE MRI and carbogen-challenge BOLD MRI can detect differential responses within a tumor that may potentially serve as noninvasive imaging biomarkers to detect microvascular changes in response to radiation therapy.

Abnormal neural activity in partially remitted late-onset depression: an fMRI study of one-back working memory task.

Only half of the geriatric patients with major depressive disorder (MDD) can reach full remission after treatment of half a year. This study was designed to examine the neural responses in the partial responders of late-onset MDD. We used 3-Tesla functional magnetic resonance imaging to assess the patterns of cerebral activation/deactivation in the performance of a one-back version of the n-back working memory task. We recruited 14 major depressive patients who reached partial remission after at least half a year of pharmacological intervention, compared with 14 non-depressive controls. There were no significant between-group differences in the demographical profiles and working memory performance, which was true for both accuracy and reaction time. Brain masks encompassing the neural responses of activation/deactivation were constructed from the non-depressive controls. The depressive group shows enhanced activities at left middle frontal and left parietal regions, and reduced deactivation at several temporal regions and left amygdala within the masks. Besides, the depressive group activates extra neural nodes at middle frontal and middle temporal regions outside the masks. The neural responses in the left amygdala are significantly correlated with the severity of depression and comorbid anxiety. The loss of deactivation in the left amygdala and the temporal areas in cognitive endeavor may be related to the refractoriness to treatment.