Lower R1 Research Articles

Ultra‐high‐resolution quantitative MRI at the grey/white interface in Alzheimer’s disease and posterior cortical atrophy

AbstractBackgroundCortical grey matter (CGM) and superficial white matter (SWM) undergo pathological changes, but standard MRI spatial resolutions make interpreting disease‐related effects at their interface challenging. We present findings from a study investigating the grey/white interface in typical amnestic Alzheimer’s disease (tAD), posterior cortical atrophy (PCA) and healthy controls using ultra‐high‐resolution quantitative MRI measures sensitive to microstructural properties.MethodEleven participants (Table 1) were scanned at 7T using multi‐echo FLASH (0.5mm isotropic resolution with prospective motion correction) and diffusion MRI (dMRI) (1.25mm isotropic resolution). The hMRI toolbox produced multi‐parametric mapping (MPM) measures: R1, R2* and Proton Density (PD) (Vaculciakova et al., 2021https://doi.org/10.1002/mrm.29253). dMRI processing included denoising and correcting for Gibbs ringing, eddy currents, susceptibility artifacts and motion. Metrics from dMRI were fractional anisotropy (FA), and mean diffusivity (MD), as well as tissue fraction (TF), neurite density index (NDI) and orientation dispersion index (ODI) from Neurite Orientation Dispersion and Density Imaging (NODDI). A deep learning segmentation approach estimated the grey/white boundary (Billot et al., 2021, arXiv:2107.09559). MPM and dMRI measures were sampled from the CGM into the SWM at 0.5mm increments in regions of interest (Harvard‐Oxford cortical atlas). Tissue‐weighted (tw) averages were calculated for NDI and ODI. Metrics were visualized across the grey/white interface using boxplots.ResultFigures 1‐2 show MPM and dMRI measures in the precuneus (dashed lines indicate group medians). Qualitatively, most tAD and PCA participants had lower R1 and R2* than controls, most prominently 0.5mm into the SWM (Figure 1). PD appeared higher in tAD and PCA patients across the grey/white interface. Qualitatively, most tAD and PCA participants had lower TF and higher MD in the CGM, where twNDI and FA appeared lower than controls across grey/white interface (Figure 2). Most tAD and PCA had qualitatively lower twODI in CGM and a flatter slope across the grey/white interface compared to controls.ConclusionMacromolecular (R1, R2* and twNDI) and iron content (R2*) MR measures at 7T appear reduced in tAD and PCA across the grey/white interface, whereas neurite organisational complexity (twODI) may become more homogeneous. Ongoing study will assess if these findings are consistent with further participants.

Lower myelin content is associated with more rapid cognitive decline among cognitively unimpaired individuals.

The influence of myelination on longitudinal changes in cognitive performance remains unclear. For each participant (N=123), longitudinal cognitive scores were calculated. Myelin content was probed using myelin water fraction (MWF) or longitudinal relaxation rate (R1 ); both are MRI measures sensitive to myelin, with MWF being specific. Lower MWF was associated with steeper declines in executive function (p<.02 in all regions) and lower R1 was associated with steeper declines in verbal fluency (p<.03 in all regions). Additionally, lower R1 was associated with steeper declines in executive function (p<.02 in all regions) and memory (p<.04 in occipital and cerebral white matter) but did not survive Bonferroni correction. We demonstrate significant relationships between myelin content and the rates of change in cognitive performance among cognitively normal individuals. These findings highlight the importance of myelin in cognitive functioning and suggest MWF and R1 as imaging biomarkers to predict cognitive changes.

Associations between gut microbial families and brain myelin in a human cohort

AbstractBackgroundWe previously reported brain myelin (Dean et al, 2017) and gut microbial composition alterations (Vogt et al, 2017) in Alzheimer’s disease (AD). Prior animal studies suggest that myelin is impacted by experimentally altered gut microbiota (Keogh et al, 2021), suggesting that gut microbiota may be linked to brain myelination. However, little is yet known about the human gut microbiome and myelin alterations in the context of AD. Here, we examined the gut‐brain association in humans using biomarker and neuroimaging data.MethodAmyloid positive (n=27) and negative (n=91) participants from the Wisconsin Alzheimer’s Disease Research Center and the Wisconsin Registry for Alzheimer’s Prevention were included based on completion of one MPnRAGE (Kecskemeti et al., 2018) scan and donation of one stool sample. Myelin was assessed using MPnRAGE‐derived quantitative R1 and myelin content in 9 white matter tracts were examined as primary outcomes (Table). Intestinal microbiota composition was characterized using 16S rRNA sequencing of fecal samples. QIIME2 was used to denoise and classify features. Phyloseq was used to filter rare taxa, compute relative abundances, and agglomerate at the family taxonomic rank, resulting in 35 microbial families used as primary predictors. Multiple regression was used to test associations between each microbial family and regional myelin content. Benjamini‐Hochberg false discovery rate (FDR) adjustment was applied post‐regression; results were considered significant at q&lt;.05.ResultMicrobial family Turicibacteraceae was positively associated with myelin indexed by R1 (Figure) in the forceps minor (b=.014, q=.037) and uncinate fasciculus (b=.011, q=.028). Across all white matter tracts, higher age was associated with lower R1. Interestingly, there was a significant Paraprevotellaceae‐by‐amyloid effect in the superior longitudinal fasciculus (b= ‐.017, p =.031) and Clostridiaceae‐by‐amyloid effect in the forceps major (b=.002, p=.037) though neither interaction survived FDR correction.ConclusionIn both the uncinate fasciculus and forceps minor, higher levels of Turicibacteraceae were associated with greater myelin content. Turicibacteraceae were previously identified as less abundant among individuals with AD; the current study’s microbial associations with large white matter tracts that are altered in AD warrants further study. Future studies will test additional metrics of AD pathology to clarify gut microbe and brain relationships.

Factors Associated with Serum Vitamin D Metabolites and Vitamin D Metabolite Ratios in Premenopausal Women.

The most representative indicator of vitamin D status in clinical practice is 25(OH)D3, but new biomarkers could improve the assessment of vitamin D status and metabolism. The objective of this study is to investigate the association of serum vitamin D metabolites and vitamin D metabolite ratios (VMRs) with potentially influential factors in premenopausal women. This is a cross-sectional study based on 1422 women, aged 39–50, recruited from a Madrid Medical Diagnostic Center. Participants answered an epidemiological and a food frequency questionnaire. Serum vitamin D metabolites were determined using an SPE–LC–MS/MS platform. The association between participant’s characteristics, vitamin D metabolites, and VMRs was quantified by multiple linear regression models. Mean 25(OH)D3 concentration was 49.2 + 18.9 nmol/L, with greater deficits among obese, nulliparous, dark-skinned women, and with less sun exposure. A lower R2 ratio (1,25(OH)2D3/25(OH)D3) and a higher R4 (24,25(OH)2D3/1,25(OH)2D3) were observed in nulliparous women, with high sun exposure, and those with low caloric intake or high consumption of calcium, vitamin D supplements, or alcohol. Nulliparous women had lower R1 (25(OH)D3/Vit D3) and R3 (24,25(OH)2D3/25(OH)D3), and older women showed lower R3 and R4. Vitamin D status modified the association of the VMRs with seasons. VMRs can be complementary indicators of vitamin D status and its endogenous metabolism, and reveal the influence of certain individual characteristics on the expression of hydroxylase enzymes.

Tau pathology and relative cerebral blood flow are independently associated with cognition in Alzheimer\u2019s disease

PurposeWe aimed to investigate associations between tau pathology and relative cerebral blood flow (rCBF), and their relationship with cognition in Alzheimer’s disease (AD), by using a single dynamic [18F]flortaucipir positron emission tomography (PET) scan.MethodsSeventy-one subjects with AD (66 ± 8 years, mini-mental state examination (MMSE) 23 ± 4) underwent a dynamic 130-min [18F]flortaucipir PET scan. Cognitive assessment consisted of composite scores of four cognitive domains. For tau pathology and rCBF, receptor parametric mapping (cerebellar gray matter reference region) was used to create uncorrected and partial volume-corrected parametric images of non-displaceable binding potential (BPND) and R1, respectively. (Voxel-wise) linear regressions were used to investigate associations between BPND and/or R1 and cognition.ResultsHigher [18F]flortaucipir BPND was associated with lower R1 in the lateral temporal, parietal and occipital regions. Higher medial temporal BPND was associated with worse memory, and higher lateral temporal BPND with worse executive functioning and language. Higher parietal BPND was associated with worse executive functioning, language and attention, and higher occipital BPND with lower cognitive scores across all domains. Higher frontal BPND was associated with worse executive function and attention. For [18F]flortaucipir R1, lower values in the lateral temporal and parietal ROIs were associated with worse executive functioning, language and attention, and lower occipital R1 with lower language and attention scores. When [18F]flortaucipir BPND and R1 were modelled simultaneously, associations between lower R1 in the lateral temporal ROI and worse attention remained, as well as for lower parietal R1 and worse executive functioning and attention.ConclusionTau pathology was associated with locally reduced rCBF. Tau pathology and low rCBF were both independently associated with worse cognitive performance. For tau pathology, these associations spanned widespread neocortex, while for rCBF, independent associations were restricted to lateral temporal and parietal regions and the executive functioning and attention domains. These findings indicate that each biomarker may independently contribute to cognitive impairment in AD.

Vascular biomarkers derived from dynamic contrast-enhanced MRI predict response of vestibular schwannoma to antiangiogenic therapy in type 2 neurofibromatosis.

BackgroundAntiangiogenic therapy of vestibular schwannoma (VS) in type 2 neurofibromatosis can produce tumor shrinkage with response rates of 40%–60%. This study examines the predictive value of parameter-derived MRI in this setting.MethodsTwelve patients with 20 VSs were recruited. Each had at least one rapidly growing tumor. Patients were treated with bevacizumab, 5 mg/kg every 2 weeks. Patients with stable or reduced VS volume were maintained at 2.5–5 mg every 4 weeks after 6 months. Those who failed treatment had their bevacizumab discontinued. Dynamic contrast-enhanced (DCE) MRI performed prior to treatment using a high temporal resolution technique, and data were analyzed to allow measurement of contrast transfer coefficient (Ktrans), vascular fraction (vp), extravascular-extracellular fraction (ve). Relaxation rate (R1N) was measured using a variable flip angle technique. Apparent diffusional coefficient (ADC) was calculated from diffusion-weighted imaging. The predictive power of microvascular parameters and ADC were examined using logistic regression modeling.ResultsResponding tumors were larger (P < .001), had lower R1N (P < .001), and higher Ktrans (P < .05) and ADC (P < .01). They showed increases in R1N (P < .01) and reduction of Ktrans (P < .01) and ADC (P < .01). Modeling to predict response demonstrated significant independent predictive power for R1N (Β = − 0.327, P < .001), and Ktrans (Β = 0.156, P < .05). Modeling to predict percentage change in tumor volume at 90 days identified baseline tumor volume (Β = 5.503, P < .05), R1N (Β = − 5.844, P < .05), and Ktrans (Β = 5.622, P < .05) as independent significant predictors.ConclusionsIn patients with type 2 neurofibromatosis, biomarkers from DCE-MRI are predictive of VS volume response to inhibition of vascular endothelial growth factor inhibition.

Improved performance of dye-sensitized solar cell with a specially tailored TiO2 compact layer prepared by RF magnetron sputtering

We demonstrate that a graded index TiO2 antireflective compact layer (arc-TiO2) employed by RF sputtering can modulate the optical transmittance and reduce the electron recombination in dye-sensitized solar cell (DSSC). The spectral response of the DSSC is improved, due to higher and red-shifted transmittance spectra in a specific region that favours the sensitization effect of the dye. The effects of arc-TiO2 prepared at various RF sputtering powers to the performances of DSSC were investigated by means of the incident photo to current efficiency (IPCE), open-circuit voltage decay (OCVD) and electrochemical impedance spectroscopy (EIS). The slow decay of the photo-voltage attributed to the desirable merits of the arc-TiO2 compact layer has been evidenced by the OCVD measurement. Meanwhile, the improvement of adhesion between an arc-TiO2 film and porous-TiO2 has decreased the interfacial-charge resistance, R1 in the EIS measurement. This lower R1 then facilitates the charge-transfer process of the electron in the DSSC. At 100W of RF power, these blended effects improved the overall conversion efficiency of the DSSC by an increase of 42% compared to the cell without the compact layer.

Neoadjuvant Therapy and Vascular Resection During Pancreaticoduodenectomy: Shifting the Survival Curve for Patients with Locally Advanced Pancreatic Cancer

Neoadjuvant therapy and vascular resection may offer patients with locally advanced pancreatic cancer potential cure. We reviewed medical records of patients with ductal adenocarcinoma who underwent pancreaticoduodenectomy (PD) from 1992 through 2011. We identified patients who received neoadjuvant therapy (NA+) or required vascular resection (VR+) for locally advanced disease and compared outcomes to those who did not. Of the 643 patients who were initially explored, 506 (143 NA+ and 363 NA- patients) ultimately underwent PD. There were no significant differences in R0 resection or morbidity. Mortality was higher in the NA+ versus NA- group (7.0 vs 3.0 %, p = 0.04). More NA+ patients underwent PD VR+ (p < 0.001). Among VR+ patients, neoadjuvant therapy resulted in significantly lower R1 resection. Among resected patients, survival of NA+ patients was significantly longer than both NA- patients (27.3 vs 19.7 months, p < 0.05) and patients abandoned because of locally advanced disease. Age, tumor grade, lymph node ratio, and R1 resection were independent predictors of poor survival. Neoadjuvant therapy and vascular resection offer patients with locally advanced pancreatic cancer the chance for cure with acceptable morbidity and mortality. These patients have improved survival over patients deemed locally inoperable by traditional criteria.

Some blood genetic characteristics of several Sudanese tribes.

The distribution of ABO and Rhesus blood groups, serum haptoglobin, and transferrin; red cell glucose-6-phosphate dehydrogenase and acid phosphatase; and hemoglobin was studied among the two aboriginal negroid tribes (Nuba and Fur); the Nilotic tribe; five tribes of Arab ancestory; and a mixed group of other minor tribes of Arab origin. The Nilotic and Nuba tribes were genetically quite distinct from the rest, with lower R1, R2, and r in the Rhesus system and low HbS and Gd-. The Arab tribes had a genetic structure which was intermediate between that of the original negroid population of the Sudan and the Arabs to the north. However, some of the Arab tribes had special genetical characteristics, e.g., Messeria had high TfD1; both Messeria and Hawazma had high HbS and Gd-, while GdA was higher only in the Hawazma. The Gaalin had very low HbS, Ro, GdA, and Gd-, suggestive of less negroid admixture compared to Messeria and Hawazma. The Fur, though an aboriginal negroid tribe, had genetic characteristics similar to Arabs.