Personalizing Deep Brain Stimulation Using Advanced Imaging Sequences.

OBJECTIVE: With a growing appreciation for interindividual anatomical variability and patient-specific brain connectivity, advanced imaging sequences offer the opportunity to directly visualize anatomical targets for deep brain stimulation (DBS). The lack of quantitative evidence demonstrating their clinical utility, however, has hindered their broad implementation in clinical practice. METHODS: Using fast gray matter acquisition T1 inversion recovery (FGATIR) sequences, the present study identified a thalamic hypointensity that holds promise as a visual marker in DBS. To validate the clinical utility of the identified hypointensity, we retrospectively analyzed 65 patients (26 female, mean age = 69.1 ± 12.7 years) who underwent DBS in the treatment of essential tremor. We characterized its neuroanatomical substrates and evaluated the hypointensity's ability to predict clinical outcome using stimulation volume modeling and voxelwise mapping. Finally, we determined whether the hypointensity marker could predict symptom improvement on a patient-specific level. RESULTS: Anatomical characterization suggested that the identified hypointensity constituted the terminal part of the dentatorubrothalamic tract. Overlap between DBS stimulation volumes and the hypointensity in standard space significantly correlated with tremor improvement (R2  = 0.16, p = 0.017) and distance to hotspots previously reported in the literature (R2  = 0.49, p = 7.9e-4). In contrast, the amount of variance explained by other anatomical atlas structures was reduced. When accounting for interindividual neuroanatomical variability, the predictive power of the hypointensity increased further (R2  = 0.37, p = 0.002). INTERPRETATION: Our findings introduce and validate a novel imaging-based marker attainable from FGATIR sequences that has the potential to personalize and inform targeting and programming in DBS for essential tremor. ANN NEUROL 2022;91:613-628.

Microstructural changes in the thalamus after mild traumatic brain injury: A longitudinal diffusion and mean kurtosis tensor MRI study.

PRIMARY OBJECTIVE: The primary aim of this study was to assess microstructural changes in the thalamus, hippocampus and corpus callosum with a fast mean kurtosis tensor (MKT) technique, in the acute and sub-acute phase after mTBI. It was hypothesized that MKT would differ between baseline and follow-up in patients. The secondary aim was to relate diffusion measures to symptoms of mTBI. RESEARCH DESIGN: A longitudinal case-control study. METHODS AND PROCEDURES: Twenty-seven patients with mTBI and 27 age- and gender-matched healthy controls were enrolled in the study. Patients were scanned within 2 weeks and 3 months after mTBI, while the controls were scanned once. MAIN OUTCOMES AND RESULTS: MKT decreased significantly (p = 0.02) from baseline to follow-up in the thalamus in patients. Compared to healthy subjects, thalamic MKT values were significantly larger in patients at baseline (p = 0.048). Secondary analysis revealed a significant decrease (p = 0.01) in fractional anisotropy in the splenium of corpus callosum from baseline to follow-up. CONCLUSIONS: The current study indicates microstructural changes in the thalamus and corpus callosum from within 14 days to 3 months after mTBI and suggests MKT as a potential biomarker after mTBI.

Automatic thalamus and hippocampus segmentation from MP2RAGE: comparison of publicly available methods and implications for DTI quantification.

PURPOSE: In both structural and functional MRI, there is a need for accurate and reliable automatic segmentation of brain regions. Inconsistent segmentation reduces sensitivity and may bias results in clinical studies. The current study compares the performance of publicly available segmentation tools and their impact on diffusion quantification, emphasizing the importance of using recently developed segmentation algorithms and imaging techniques. METHODS: Four publicly available, automatic segmentation methods (volBrain, FSL, FreeSurfer and SPM) are compared to manual segmentation of the thalamus and hippocampus imaged with a recently proposed T1-weighted MRI sequence (MP2RAGE). We evaluate morphometric accuracy on 22 healthy subjects and impact on diffusivity measurements obtained from aligned diffusion-weighted images on a subset of 10 subjects. RESULTS: Compared to manual segmentation, the highest Dice similarity index of the thalamus is obtained with volBrain using a local library ([Formula: see text], [Formula: see text]) followed by volBrain using an external library ([Formula: see text], [Formula: see text]), FSL ([Formula: see text], [Formula: see text]), FreeSurfer ([Formula: see text], [Formula: see text]) and SPM ([Formula: see text], [Formula: see text]). The same order is found for hippocampus with volBrain local ([Formula: see text], [Formula: see text]), volBrain external ([Formula: see text], [Formula: see text]), FSL ([Formula: see text], [Formula: see text]), FreeSurfer ([Formula: see text], [Formula: see text]) and SPM ([Formula: see text], [Formula: see text]). For diffusivity measurements, volBrain provides values closest to those obtained from manual segmentations. volBrain is the only method where FA values do not differ significantly from manual segmentation of the thalamus. CONCLUSIONS: Overall we find that volBrain is superior in thalamus and hippocampus segmentation compared to FSL, FreeSurfer and SPM. Furthermore, the choice of segmentation technique and training library affects quantitative results from diffusivity measures in thalamus and hippocampus.

Effect of thyroxine on brain microstructure in extremely premature babies: magnetic resonance imaging findings in the TIPIT study.

BACKGROUND: In order to assess relationships between thyroid hormone status and findings on brain MRI, a subset of babies was recruited to a multi-centre randomised, placebo-controlled trial of levothyroxine (LT4) supplementation for babies born before 28 weeks' gestation (known as the TIPIT study, for Thyroxine supplementation In Preterm InfanTs). These infants were imaged at term-equivalence. MATERIALS AND METHODS: Forty-five TIPIT participants had brain MRI using diffusion tensor imaging (DTI) to estimate white matter development by apparent diffusion coefficient (ADC), fractional anisotropy (FA) and tractography metrics of number and length of streamlines. We made comparisons between babies with the lowest and highest plasma FT4 concentrations during the initial 4 weeks after birth. RESULTS: There were no differences in DTI metrics between babies who had received LT4 supplementation and those who had received a placebo. Among recipients of a placebo, babies in the lowest quartile of plasma-free thyroxine (FT4) concentrations had significantly higher apparent diffusion coefficient measurements in the posterior corpus callosum and streamlines that were shorter and less numerous in the right internal capsule. Among LT4-supplemented babies, those who had plasma FT4 concentrations in the highest quartile had significantly lower apparent diffusion coefficient values in the left occipital lobe, higher fractional anisotropy in the anterior corpus callosum and longer and more numerous streamlines in the anterior corpus callosum. CONCLUSION: DTI variables were not associated with allocation of placebo or thyroid supplementation. Markers of poorly organised brain microstructure were associated with low plasma FT4 concentrations after birth. The findings suggest that plasma FT4 concentrations affect brain development in very immature infants and that the effect of LT4 supplementation for immature babies with low FT4 plasma concentrations warrants further study.

The development and psychometric assessment of a questionnaire to assess sleep and daily troubles in parents of children and young adults with severe psychomotor impairment.

BACKGROUND: Children with severe psychomotor impairment (SPMI) often experience sleep disturbances that severely distress both the child and his or her parents. Validated questionnaires for the assessment of parents' distress related to their child's sleep disturbances are lacking. METHODS: We developed and validated a new questionnaire, the HOST (holistic assessment of sleep and daily troubles in parents of children with SPMI) to assess the effect of the sleep disturbances in children with SPMI on their parents. The questionnaire was developed based on published data and expert opinion, and it was refined via direct consultation with affected parents. Its psychometric characteristics were assessed in a sample of parents of 214 children with SPMI. It was retested using a random subsample of the participants. RESULTS: Explorative factor analysis revealed that the HOST was composed of four scales. Fit indices, item analysis, and convergent validity (coherence with preexisting instruments of sleep disturbances and health status) were adequate. Retest analysis (n=62) revealed high stability of the HOST questionnaire and adequate replication validity. CONCLUSION: Sleep-related difficulties significantly impact the sociomedical characteristics of the parents of children with complex neurologic diseases. Typically, parents are severely affected in various aspects of daily life (i.e., medical health, social life, professional life). The HOST proved to be a valid, reliable and economical assessment tool of sleep-related difficulties in parents and relatives of children with SPMI. The HOST is capable of identifying individuals and specific areas requiring intervention.

Changes in 3-dimensional bone structure indices in hypoparathyroid patients treated with PTH(1-84): a randomized controlled study.

Hypoparathyroidism (hypoPT) is characterized by a state of low bone turnover and high bone mineral density (BMD) despite conventional treatment with calcium supplements and active vitamin D analogues. To assess effects of PTH substitution therapy on 3-dimensional bone structure, we randomized 62 patients with hypoPT into 24 weeks of treatment with either PTH(1-84) 100 µg/day subcutaneously or similar placebo as an add-on therapy. Micro-computed tomography was performed on 44 iliac crest bone biopsies (23 on PTH treatment) obtained after 24 weeks of treatment. Compared with placebo, PTH caused a 27% lower trabecular thickness (p < 0.01) and 4% lower trabecular bone tissue density (p < 0.01), whereas connectivity density was 34% higher (p < 0.05). Trabecular tunneling was evident in 11 (48%) of the biopsies from the PTH group. Patients with tunneling had significantly higher levels of biochemical markers of bone resorption and formation. At cortical bone, number of Haversian canals per area was 139% higher (p = 0.01) in the PTH group, causing a tendency toward an increased cortical porosity (p = 0.09). At different subregions of the hip, areal BMD (aBMD) and volumetric BMD (vBMD), as assessed by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT), decreased significantly by 1% to 4% in the PTH group. However, at the lumbar spine, aBMD decreased by 1.8% (p < 0.05), whereas vBMD increased by 12.8% (p = 0.02) in the PTH compared with the placebo group.

Reduced prediagnostic 25-hydroxyvitamin D levels in women with breast cancer: a nested case-control study.

Vitamin D status may affect risk of cancer. In a cross-sectional study with a nested case-control analysis, we determined whether risk of breast cancer is associated with prediagnostic plasma 25-hydroxyvitamin D (25OHD) levels and the effects of lifestyle characteristics known to influence vitamin D status on risk of breast cancer. We studied women without a prior history of breast cancer referred to a diagnostic mammography examination (n = 2,465). Cases were women diagnosed with an incident breast cancer (n = 142). Controls were women not diagnosed with a breast cancer matched to cases on age, menopausal status, and time of year of blood sampling (n = 420). Characteristics of cases and controls were assessed by a self-administrated questionnaire. Blood samples were collected prior to the diagnostic mammography examination. Cases had lower plasma 25OHD levels than controls. Compared with the lowest tertile of 25OHD levels, risk of breast cancer was significantly reduced among women in the highest tertile (relative risk, 0.52; 95% confidence interval, 0.32-0.85). Risk estimates were similar in women with an estrogen receptor-positive and estrogen receptor-negative breast cancer. Use of vitamin D supplements, sunbathing frequency, and fish intake was associated with 25OHD levels, but did not affect the risk of breast cancer. Accordingly, risk of breast cancer was inversely associated with 25OHD levels. Randomized controlled trials are warranted in order to assess whether a causal relationship exists.