Relaxation Along a Fictitious Field, continuous wave T1rho, adiabatic T1rho and adiabatic T2rho imaging of human gliomas at 3T: A feasibility study.

In pre-clinical models of brain gliomas, Relaxation Along a Fictitious Field in second rotating frame (TRAFF2), continues wave T1rho (T1ρcw), adiabatic T1rho (T1ρadiab), and adiabatic T2rho (T2ρadiab) relaxation time mappings have demonstrated potential to non-invasively characterize brain gliomas. Our aim was to evaluate the feasibility and potential of 4 different spin lock methods at 3T to characterize primary brain glioma. 22 patients (26-72 years) with suspected primary glioma. T1ρcw was performed using pulse peak amplitude of 500Hz and pulse train durations of 40 and 80 ms while the corresponding values for T1ρadiab, T2ρadiab, TRAFF2 were 500/500/500Hz and 48 and 96, 64 and 112, 45 and 90 ms, respectively. The parametric maps were calculated using a monoexponential model. Molecular profiles were evaluated from tissue specimens obtained during the resection. The lesion regions-of-interest were segmented from high intensity FLAIR using automatic segmentation with manual refinement. Statistical descriptors from the voxel intensity values inside each lesion and radiomic features (Pyrad MRC package) were calculated. From extracted radiomics, mRMRe R package version 2.1.0 was used to select 3 features in each modality for statistical comparisons. Of the 22 patients, 10 were found to have IDH-mutant gliomas and of those 5 patients had 1p/19q codeletion group comparisons. Following correction for effects of age and gender, at least one statistical descriptor was able to differentiate between IDH and 1p/19q codeletion status for all the parametric maps. In the radiomic analysis, corner-edge detector features with Harris-Stephens filtered signal showed significant group differences in IDH and 1p/19q codeletion groups. Spin lock imaging at 3T of human glioma was feasible and various qualitative parameters derived from the parametric maps were found to have potential to differentiate IDH and 1p19q codeletion status. Future larger prospective clinical trials are warranted to evaluate these methods further.

S-[18F]THK-5117-PET and [11C]PIB-PET Imaging in Idiopathic Normal Pressure Hydrocephalus in Relation to Confirmed Amyloid-ß Plaques and Tau in Brain Biopsies.

BACKGROUND: Detection of pathological tau aggregates could facilitate clinical diagnosis of Alzheimer's disease (AD) and monitor drug effects in clinical trials. S-[18F]THK-5117 could be a potential tracer to detect pathological tau deposits in brain. However, no previous study have correlated S-[18F]THK-5117 uptake in PET with brain biopsy verified tau pathology in vivo. OBJECTIVE: Here we aim to evaluate the association between cerebrospinal fluid (CSF) AD biomarkers, S-[18F]THK-5117, and [11C]PIB PET against tau and amyloid lesions in brain biopsy. METHODS: Fourteen patients with idiopathic normal pressure hydrocephalus (iNPH) with previous shunt surgery including right frontal cortical brain biopsy and CSF Aß1 - 42, total tau, and P-tau181 measures, underwent brain MRI, [11C]PIB PET, and S-[18F]THK-5117 PET imaging. RESULTS: Seven patients had amyloid-ß (Aß, 4G8) plaques, two both Aß and phosphorylated tau (Pτ, AT8) and one only Pτ in biopsy. As expected, increased brain biopsy Aß was well associated with higher [11C]PIB uptake in PET. However, S-[18F]THK-5117 uptake did not show any statistically significant correlation with either brain biopsy Pτ or CSF P-tau181 or total tau. CONCLUSIONS: S-[18F]THK-5117 lacked clear association with neuropathologically verified tau pathology in brain biopsy probably, at least partially, due to off-target binding. Further studies with larger samples of patients with different tau tracers are urgently needed. The detection of simultaneous Aß and tau pathology in iNPH is important since that may indicate poorer and especially shorter response for CSF shunt surgery compared with no pathology.

Consumer consciousness on meat and the environment - Exploring differences.

Global environmental challenges require changes in both the production and the consumption of goods. In this paper we analyse how consumers perceive the high environmental burden of meat. We analysed consumer environmental consciousness, including problem awareness and a support to action dimensions, latter including perceived self-efficacy as well as solutions to problems. The solutions were positioned on a continuum from increasing the efficiency of production to discussing sufficiency levels in consumption practices (techno-optimism, local meat, organic meat and meat reduction, respectively). We used a statistically representative survey sample (n = 1890) from the population of Finland and cluster analysis to explore differences among consumers. The analysis revealed that most Finns seem to be rather unsure of the study topic. At the same time they tend to have a comparably high level of self-efficacy (55 per cent of respondents) and endorsement of particularly local meat solution type (55%), followed by organic meat (35%), meat reduction (25%) and techno-optimism (15%), though the neutral stand was the most common one across the data. We also identified six consumer groups that reveal not only a high number of Highly unsure consumers (40%), but also some Rather conscious (20%) and a relatively small number of Highly conscious (8%). In addition, there were also easily observable groups of Careless conscious (14%), Rather unsure (9%) and Resistant (8%). The results highlight the need for a multitude of political actions to guide meat consumption, as there are groups that may benefit from practical tools for making dietary changes as well as groups in need for more comprehensive selection of measures, including environmental information.

Striatal volume is related to phonemic verbal fluency but not to semantic or alternating verbal fluency in early Parkinson's disease.

Verbal fluency impairments are frequent in Parkinson's disease (PD) and they may be present already at early stages. Semantic fluency impairment is associated with Parkinson's disease dementia and temporal, frontal and cerebellar cortical changes. Few studies have addressed cerebral structural correlates of different verbal fluency tasks in early stage PD. We therefore studied gray matter volumes of T1-weighted MRI images using voxel-based morphometry in relation to semantic, phonemic, and alternating verbal fluency in younger (mean age <65 years), early stage (mean disease duration <3 years), non-demented PD patients (n = 28) and healthy controls (n = 27). We found a significant association between worse phonemic fluency and smaller striatal, namely right caudate gray matter volume in the PD group only (family-wise error corrected p = 0.007). Reduced semantic fluency was associated with smaller gray matter volumes in left parietal cortex (p = 0.037) and at trend level with smaller bilateral cerebellum gray matter volume across groups (p = 0.062), but not in the separate PD or control groups. There were no significant relationships between alternating fluency and gray matter volumes in the whole sample or in the groups separately. The fact that phonemic fluency, but not semantic or alternating fluency, was associated with caudate gray matter volume at early stage PD suggests that different fluency tasks rely on different neural substrates, and that language networks supporting semantic search and verbal-semantic switching are unrelated to brain gray matter volume at early disease stages in PD.

Brain volumetric correlates of memory in early Parkinson's disease.

BACKGROUND: Free recall memory deficits are common in Parkinson's disease (PD), even at early stages before mild cognitive impairment or dementia. Their association with brain structural changes has not been established. OBJECTIVE: We studied local gray matter volumes in relation to different memory tasks in early stage PD. METHODS: Magnetic resonance images (MRI) and neuropsychological data were obtained from 28 non-demented, medicated PD patients, and 28 healthy controls. The gray matter segments of T1-weighted MRI images were analyzed using voxel-based morphometry in relation to visual and verbal memory tasks. Measures of immediate free recall, verbal learning, delayed recall and memory consolidation were obtained. A novel measure of incidental memory was included. RESULTS: Patients and controls showed no significant group differences in local gray matter volumes. Voxel-based morphometry analyses revealed that worse performance on an incidental visual memory task was associated with smaller right parietal gray matter volume (Family-wise error corrected P = 0.002). This association was present in the PD group (corrected P = 0.005), but not in controls (corrected P > 0.99). No associations between gray matter volumes and the other memory tasks were found in either group. CONCLUSIONS: The results suggest that right parietal cortical gray matter volume is related to free recall memory deficits in early stage PD in conditions not involving an intention to memorize visual items. This preliminary finding needs to be established in further studies utilizing incidental memory tasks in PD.

Cognitive slowing in Parkinson's disease is related to frontostriatal dopaminergic dysfunction.

BACKGROUND: Frontostriatal and cognitive dysfunctions in Parkinson's disease (PD) are hypothesized to be linked predominately to dopaminergic dysfunction within neural networks linking dorsal striatum to dorsolateral prefrontal cortex. METHODS: The authors evaluated the relationship between frontostriatal dopaminergic function and cognitive performance, especially cognitive processing speed by performing [(18)F]fluorodopa PET and computerized tests of automatic and controlled cognitive processing speed (CogniSpeed) in 23 newly diagnosed and unmedicated PD patients and 14 controls. RESULTS: PD patients were slower than the controls in all the CogniSpeed measures studied. The Fdopa uptake in caudate nucleus correlated negatively with slowing on all the tests. Slower performance in relatively automatic processes measured by choice reaction tasks as well as in more controlled processes measured by a calculation task was related to reduced Fdopa uptake in the anterior cingulate gyrus. The reduced dopaminergic function in the thalamus was associated with the slower performance in the subtraction test. CONCLUSION: Our study indicates that dopaminergic dysfunction within neural networks linking striatum to prefrontal cortex is involved in the slowing of both automatic and controlled cognitive processing in PD patients.

Seasonality of striatal dopamine synthesis capacity in Parkinson's disease.

Recent neuroimaging evidence suggests that the healthy human brain dopaminergic system may show seasonal rhythmicity, as striatal dopamine synthesis capacity has been reported to be higher during fall and winter. There is additional evidence about season of birth effects on morbidity in several neuropsychiatric disorders. We investigated possible seasonal changes in dopamine synthesis capacity in a relatively large sample of Parkinson's disease patients. 6-[(18)F]fluoro-l-DOPA brain PET scans for 109 Parkinson's disease patients were performed during different seasons and the effects of season of scanning and season of birth on striatal tracer uptake were studied, controlling for covariates such as age, sex and disease severity. The patients scanned during fall and winter had 15% higher tracer uptake in the right putamen compared to patients scanned during spring and summer (p=0.04). Patients born during winter and spring had 10% higher dopamine synthesis capacity in the left caudate (p=0.008), 8% higher capacity in the right caudate (p=0.04) and 16% higher capacity in the putamen contralateral to the side of predominant motor symptoms (p=0.02) compared to patients born during summer and fall (after correcting for differences in age, sex, disease severity, scanner and season of scanning). The results suggest that there are seasonal oscillations also in the hypoactive dopaminergic system of Parkinson's disease patients. Findings concerning season of birth further suggest that there may be gestational or perinatal seasonal factors, which influence dopaminergic function in adulthood.

[(11)C]PIB-, [(18)F]FDG-PET and MRI imaging in patients with Parkinson's disease with and without dementia.

The objective of this study was to identify possible group differences between PD patients with dementia and without dementia by combining different functional and structural imaging methods in vivo, which might provide an opportunity to disentangle the pathophysiological correlates of cognitive impairment and dementia in PD. We performed a neuropsychological evaluation, structural brain MRI, [(18)F]FDG PET and [(11)C]PIB PET in 19 PD patients [eight non-demented (PD), eleven demented (PDD)] and 24 healthy elderly volunteers. [(11)C]PIB region-to-cerebellum ratios did not differ significantly between the groups in any brain region (p > 0.05). PDD patients showed impaired glucose metabolism in cortical brain regions and this reduction was associated with the degree of cognitive impairment. PDD patients had more atrophy both in the hippocampus and the frontal cortex compared with PD patients and controls, and hippocampal atrophy was associated with impaired memory. This cross-sectional data suggests that development of dementia in PD is associated with extensive spread of hypometabolism beyond the occipital cortex, and with hippocampal and frontal atrophy but not beta-amyloid deposition consistent with a unique biological process related to PD rather than co-incidental development of AD in persons with PD.

Simple ratio analysis of 18F-fluorodopa uptake in striatal subregions separates patients with early Parkinson disease from healthy controls.

UNLABELLED: 6-(18)F-fluoro-l-dopa ((18)F-FDOPA) is widely used to investigate dopaminergic hypofunction, for instance, in Parkinson disease (PD). Conventionally, a 90-min scan with either a graphical or a metabolite-purified plasma input approach has been used for quantification. In the clinical setting, to increase compliance, especially in patients with more advanced disease, and to increase the efficacy of tracer and scanner time use, a shorter acquisition and a simple quantitative analysis are desirable. Taking into account the asymmetry of clinical symptoms and the uneven distribution of striatal dopaminergic hypofunction may also improve the use of (18)F-FDOPA PET in early disease detection. Therefore, we compared subregional striatal (18)F-FDOPA PET data from a large group of nonmedicated patients with early PD and a set of healthy elderly volunteers to find out whether a simple ratio approach would reliably separate PD patients from healthy controls. METHODS: A total of 89 nonmedicated patients with early PD and 21 healthy volunteers were studied with (18)F-FDOPA PET, and both a region-to-reference (striatal-to-occipital) ratio (SOR) calculated from 75 to 90 min after injection and a graphical analysis of data calculated from 15 to 90 min after (18)F-FDOPA injection (yielding the influx constant [K(i)(ref)]) were used. RESULTS: Both SOR and K(i)(ref) values in the PD patients were lowest, relative to those in the healthy controls, in the posterior putamen contralateral to the side with predominant clinical symptoms. The contralateral posterior putamen showed the largest areas under the receiver operating characteristic (ROC) curve-0.994 for SOR and 0.998 for K(i)(ref)-indicating excellent separation of the PD and control groups. The caudate nucleus and the ventral striatum were less impressive in this respect. CONCLUSION: A single 15-min scan 75 min after tracer injection seems to be sufficient for separating patients with PD from healthy controls in a clinical research environment. This method represents a powerful and economical alternative for research on the disease mechanism and differential diagnosis.

Impaired cognitive performance in Parkinson's disease is related to caudate dopaminergic hypofunction and hippocampal atrophy.

Frontal lobe dysfunction and other cognitive deficits have been described in Parkinson's disease (PD), which may lead to dementia. Both striatal dopaminergic deficiency and regional or global brain volume loss have been suggested to contribute to cognitive decline in PD. We therefore performed a neuropsychological evaluation, structural brain MRI and Fdopa PET in patients with PD and healthy elderly volunteers. PD patients had impaired cognitive performance in many neuropsychological tests compared to controls, not limited just to frontal lobe function tests. Caudate Fdopa correlated positively with performance in verbal (immediate and delayed) and visual memory. Patients with PD showed atrophy in the hippocampus and the prefrontal cortex and hippocampal atrophy was related to impaired memory. Our findings suggest that striatal dopaminergic depletion and global brain volume loss contribute to cognitive impairment in non-demented PD patients, but dysfunction of extra-striatal dopaminergic or non-dopaminergic systems probably plays a role especially in more generalized cognitive impairment.