A Low-Intensity Transcranial Focused Ultrasound Parameter Exploration Study of the Ventral Capsule/Ventral Striatum.

OBJECTIVES: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is effective for treatment-resistant obsessive-compulsive disorder (OCD); however, DBS is associated with neurosurgical risks. Transcranial focused ultrasound (tFUS) is a newer form of noninvasive (ie, nonsurgical) stimulation that can modulate deeper regions, such as the VC/VS. tFUS parameters have just begun to be studied and have often not been compared in the same participants. We explored the effects of three VC/VS tFUS protocols and an entorhinal cortex (ErC) tFUS session on the VC/VS and cortico-striato-thalamo-cortical circuit (CSTC) in healthy individuals for later application to patients with OCD. MATERIALS AND METHODS: Twelve individuals participated in a total of 48 sessions of tFUS in this exploratory multisite, within-subject parameter study. We collected resting-state, reward task, and arterial spin-labeled (ASL) magnetic resonance imaging scans before and after ErC tFUS and three VC/VS tFUS sessions with different pulse repetition frequencies (PRFs), pulse widths (PWs), and duty cycles (DCs). RESULTS: VC/VS protocol A (PRF = 10 Hz, PW = 5 ms, 5% DC) was associated with increased putamen activation during a reward task (p = 0.003), and increased VC/VS resting-state functional connectivity (rsFC) with the anterior cingulate cortex (p = 0.022) and orbitofrontal cortex (p = 0.004). VC/VS protocol C (PRF = 125 Hz, PW = 4 ms, 50% DC) was associated with decreased VC/VS rsFC with the putamen (p = 0.017), and increased VC/VS rsFC with the globus pallidus (p = 0.008). VC/VS protocol B (PRF = 125 Hz, PW = 0.4 ms, 5% DC) was not associated with changes in task-related CSTC activation or rsFC. None of the protocols affected CSTC ASL perfusion. CONCLUSIONS: This study began to explore the multidimensional parameter space of an emerging form of noninvasive brain stimulation, tFUS. Our preliminary findings in a small sample suggest that VC/VS tFUS should continue to be investigated for future noninvasive treatment of OCD.

Body size interacts with the structure of the central nervous system: A multi-center in vivo neuroimaging study.

Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject's sex and age. However, corrections for body size (i.e. height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1±6.6 years old, 125 females). We show that body height correlated strongly or moderately with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44≤r≤0.62). In comparison, age correlated weakly with cortical GM volume, precentral GM volume, and cortical thickness (-0.21≥r≥-0.27). Body weight correlated weakly with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20≥r≥-0.23). Body weight further correlated weakly with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r=-0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlated strongly or moderately with brain volumes (0.39≤r≤0.64), and weakly with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22≥r≥-0.25). Linear mixture of sex and age explained 26±10% of data variance in brain volumetry and SC CSA. The amount of explained variance increased at 33±11% when body height was added into the mixture model. Age itself explained only 2±2% of such variance. In conclusion, body size is a significant biological variable. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure.

Apparent diffusion coefficient values predict response to brachytherapy in bulky cervical cancer.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DWI) provides a measurement of tumor cellularity. We evaluated the potential of apparent diffusion coefficient (ADC) values obtained from post-external beam radiation therapy (EBRT) DWI and prior to brachytherapy (BT) to predict for complete metabolic response (CMR) in bulky cervical cancer. METHODS: Clinical and DWI (b value = 500 s/mm2) data were obtained from patients undergoing interstitial BT with high-risk clinical target volumes (HR-CTVs) > 30 cc. Volumes were contoured on co-registered T2 weighted images and 90th percentile ADC values were calculated. Patients were stratified by CMR (defined by PET-CT at three months post-BT). Relation of CMR with 90th percentile ADC values and other clinical factors (International Federation of Gynecology and Obstetrics (FIGO) stage, histology, tumor and HR-CTV size, pre-treatment hemoglobin, and age) was assessed both in univariate and multivariate logistic regression analyses. Youden's J statistic was used to identify a threshold value. RESULTS: Among 45 patients, twenty-eight (62%) achieved a CMR. On univariate analysis for CMR, only 90th percentile ADC value was significant (p = 0.029) while other imaging and clinical factors were not. Borderline significant factors were HR-CTV size (p = 0.054) and number of chemotherapy cycles (p = 0.078). On multivariate analysis 90th percentile ADC (p < 0.0001) and HR-CTV size (p < 0.003) were highly significant. Patients with 90th percentile ADC values above 2.10 × 10- 3 mm2/s were 5.33 (95% CI, 1.35-24.4) times more likely to achieve CMR. CONCLUSIONS: Clinical DWI may serve to risk-stratify patients undergoing interstitial BT for bulky cervical cancer.

Sludge-based candidate reference materials for enhanced quality control of particulate processes in total organic carbon analysis for wastewater1.

Accurate analyses of total organic carbon (TOC) encompassing particulate organic carbon in wastewater are key for evaluating the behavior of particulate organic contaminants and maintaining the carbon mass balance throughout the wastewater treatment process. This study was conducted to develop candidate reference materials of environmental origin from excess sludge collected from wastewater treatment facilities, primarily receiving industrial wastewater and livestock manure as the main sources. Homogeneity and stability assessments for total carbon (TC) and TOC were conducted in the particle samples following the standardized procedures of ISO Guide 35 and ISO 13258. The results showed that high inorganic carbon (IC) content in particles, such as YJ(500) (IC: 29%), rendered them unsuitable for TOC quality control (QC), as they increased uncertainty in both homogeneity and stability assessments. Additionally, a13C NMR analysis revealed that samples with a high (O-alkyl)/(C-H-alkyl) ratio in their carbon structures exhibited relatively low stability. Through the homogeneity and stability assessments, a particle sample, YJ(100), was selected as the reference material (RM); the assigned values were as follows: 30.78% for TC and 27.94% for TOC, with uncertainties of 0.01% and 1.1%, respectively. Furthermore, considering sample transportation conditions, the safe storage period for the RM particles was determined to be 2 weeks under harsh conditions (at 40 °C). In our inter-laboratory test (n = 8) using the particle samples, we confirmed that the particle samples can effectively enhance particle processing QC and validate a proposed suspended solids pretreatment method. This study showcases valuable environmental particle sample production and evaluation, offering potential advancements in the QC of TOC analysis for wastewater samples.