Characteristic BOLD signals are detectable in white matter of the spinal cord at rest and after a stimulus.

We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions.

Whole-brain, gray, and white matter time-locked functional signal changes with simple tasks and model-free analysis.

Recent studies have revealed the production of time-locked blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signals throughout the entire brain in response to tasks, challenging the existence of sparse and localized brain functions and highlighting the pervasiveness of potential false negative fMRI findings. "Whole-brain" actually refers to gray matter, the only tissue traditionally studied with fMRI. However, several reports have demonstrated reliable detection of BOLD signals in white matter, which have previously been largely ignored. Using simple tasks and analyses, we demonstrate BOLD signal changes across the whole brain, in both white and gray matters, in similar manner to previous reports of whole brain studies. We investigated whether white matter displays time-locked BOLD signals across multiple structural pathways in response to a stimulus in a similar manner to the cortex. We find that both white and gray matter show time-locked activations across the whole brain, with a majority of both tissue types showing statistically significant signal changes for all task stimuli investigated. We observed a wide range of signal responses to tasks, with different regions showing different BOLD signal changes to the same task. Moreover, we find that each region may display different BOLD responses to different stimuli. Overall, we present compelling evidence that, just like all gray matter, essentially all white matter in the brain shows time-locked BOLD signal changes in response to multiple stimuli, challenging the idea of sparse functional localization and the prevailing wisdom of treating white matter BOLD signals as artifacts to be removed.

Quantification of mediation effects of white matter functional characteristics on cognitive decline in aging.

Cognitive decline with aging involves multifactorial processes, including changes in brain structure and function. This study focuses on the role of white matter functional characteristics, as reflected in blood oxygenation level-dependent signals, in age-related cognitive deterioration. Building on previous research confirming the reproducibility and age-dependence of blood oxygenation level-dependent signals acquired via functional magnetic resonance imaging, we here employ mediation analysis to test if aging affects cognition through white matter blood oxygenation level-dependent signal changes, impacting various cognitive domains and specific white matter regions. We used independent component analysis of resting-state blood oxygenation level-dependent signals to segment white matter into coherent hubs, offering a data-driven view of white matter's functional architecture. Through correlation analysis, we constructed a graph network and derived metrics to quantitatively assess regional functional properties based on resting-state blood oxygenation level-dependent fluctuations. Our analysis identified significant mediators in the age-cognition relationship, indicating that aging differentially influences cognitive functions by altering the functional characteristics of distinct white matter regions. These findings enhance our understanding of the neurobiological basis of cognitive aging, highlighting the critical role of white matter in maintaining cognitive integrity and proposing new approaches to assess interventions targeting cognitive decline in older populations.

The Prostate Cancer Active Lifestyle Study (PALS): A randomized controlled trial of diet and exercise in overweight and obese men on active surveillance.

BACKGROUND: Active surveillance (AS) is increasingly used to monitor patients with lower risk prostate cancer (PCa). The Prostate Cancer Active Lifestyle Study (PALS) was a randomized controlled trial to determine whether weight loss improves obesity biomarkers on the causal pathway to progression in patients with PCa on AS. METHODS: Overweight/obese men (body mass index >25 kg/m2) diagnosed with PCa who elected AS were recruited. The intervention was a 6-month, individually delivered, structured diet and exercise program adapted from the Diabetes Prevention Program with a 7% weight loss goal from baseline. Control participants attended one session reviewing the US Dietary and Physical Activity Guidelines. The primary outcome was change in glucose regulation from baseline to the end of the 6-month intervention, which was measured by fasting plasma glucose, C-peptide, insulin, insulin-like growth factor 1, insulin-like growth factor binding protein-3, adiponectin, and homeostatic model assessment for insulin resistance. RESULTS: Among 117 men who were randomized, 100 completed the trial. The mean percentage weight loss was 7.1% and 1.8% in the intervention and control arms, respectively (adjusted between-group mean difference, -6.0 kg; 95% confidence interval, -8.0, -4.0). Mean percentage changes from baseline for insulin, C-peptide, and homeostatic model assessment for insulin resistance in the intervention arm were -23%, -16%, and -25%, respectively, compared with +6.9%, +7.5%, and +6.4%, respectively, in the control arm (all p for intervention effects ≤ .003). No significant between-arm differences were detected for the other biomarkers. CONCLUSIONS: Overweight/obese men with PCa undergoing AS who participated in a lifestyle-based weight loss intervention successfully met weight loss goals with this reproducible lifestyle intervention and experienced improvements in glucose-regulation biomarkers associated with PCa progression.

Interstate Telemedicine for Urologic Cancer Care.

PURPOSE: US states eased licensing restrictions on telemedicine during the COVID-19 pandemic, allowing interstate use. As waivers expire, optimal uses of telemedicine must be assessed to inform policy, legislation, and clinical care. We assessed whether telemedicine visits provided the same patient experience as in-person visits, stratified by in- vs out-of-state residence, and examined the financial burden. MATERIALS AND METHODS: Patients seen in person and via telemedicine for urologic cancer care at a major regional cancer center received a survey after their first appointment (August 2019-June 2022) on satisfaction with care, perceptions of communication during their visit, travel time, travel costs, and days of work missed. RESULTS: Surveys were completed for 1058 patient visits (N = 178 in-person, N = 880 telemedicine). Satisfaction rates were high for all visit types, both interstate and in-state care (mean score 60.1-60.8 [maximum 63], P > .05). More patients convening interstate telemedicine would repeat that modality (71%) than interstate in-person care (61%) or in-state telemedicine (57%). Patients receiving interstate care had significantly higher travel costs (median estimated visit costs $200, IQR $0-$800 vs median $0, IQR $0-$20 for in-state care, P < .001); 55% of patients receiving interstate in-person care required plane travel and 60% required a hotel stay. CONCLUSIONS: Telemedicine appointments may increase access for rural-residing patients with cancer. Satisfaction outcomes among patients with urologic cancer receiving interstate care were similar to those of patients cared for in state; costs were markedly lower. Extending interstate exemptions beyond COVID-19 licensing waivers would permit continued delivery of high-quality urologic cancer care to rural-residing patients.

Detection of Treatment Response in Triple-Negative Breast Tumors to Paclitaxel Using MRI Cell Size Imaging.

BACKGROUND: Breast cancer treatment response evaluation using the response evaluation criteria in solid tumors (RECIST) guidelines, based on tumor volume changes, has limitations, prompting interest in novel imaging markers for accurate therapeutic effect determination. PURPOSE: To use MRI-measured cell size as a new imaging biomarker for assessing chemotherapy response in breast cancer. STUDY TYPE: Longitudinal; animal model. STUDY POPULATION: Triple-negative human breast cancer cell (MDA-MB-231) pellets (4 groups, n = 7) treated with dimethyl sulfoxide (DMSO) or 10 nM of paclitaxel for 24, 48, and 96 hours, and 29 mice with MDA-MB-231 tumors in right hind limbs treated with paclitaxel (n = 16) or DMSO (n = 13) twice weekly for 3 weeks. FIELD STRENGTH/SEQUENCE: Oscillating gradient spin echo and pulsed gradient spin echo sequences at 4.7 T. ASSESSMENT: MDA-MB-231 cells were analyzed using flowcytometry and light microscopy to assess cell cycle phases and cell size distribution. MDA-MB-231 cell pellets were MR imaged. Mice were imaged weekly, with 9, 6, and 14 being sacrificed for histology after MRI at weeks 1, 2, and 3, respectively. Microstructural parameters of tumors/cell pellets were derived by fitting diffusion MRI data to a biophysical model. STATISTICAL TESTS: One-way ANOVA compared cell sizes and MR-derived parameters between treated and control samples. Repeated measures 2-way ANOVA with Bonferroni post-tests compared temporal changes in MR-derived parameters. A P-value <0.05 was considered statistically significant. RESULTS: In vitro experiments showed that the mean MR-derived cell sizes of paclitaxel-treated cells increased significantly with a 24-hours treatment and decreased (P = 0.06) with a 96-hour treatment. For in vivo xenograft experiments, the paclitaxel-treated tumors showed significant decreases in cell size at later weeks. MRI observations were supported by flowcytometry, light microscopy, and histology. DATA CONCLUSIONS: MR-derived cell size may characterize the cell shrinkage during treatment-induced apoptosis, and may potentially provide new insights into the assessment of therapeutic response. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 4.

NCCN Guidelines® Insights: Kidney Cancer, Version 2.2024.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on the systemic therapy options for patients with advanced RCC and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Kidney Cancer.

Urgent versus elective surgical disparities among American Indian and Alaska Native patients.

BACKGROUND: American Indian and Alaska Native (AIAN) health issues are understudied despite documentation of lower-than-average life expectancy. Urgent surgery is associated with higher rates of postsurgical complications and postoperative death. We assess whether American Indian and Alaska Native (AIAN) patients in Washington State are at greater risk of requiring urgent rather than elective surgery compared with non-Hispanic Whites (NHW). METHODS: We accessed data for the period 2009-2014 from the Washington State Comprehensive Hospital Abstract Reporting System (CHARS) database, which captures all statewide hospital admissions, to examine three common surgeries that are performed both urgently and electively: hip replacements, aortic valve replacements, and spinal fusions. We extracted patient race, age, insurance status, comorbidity, admission type, and procedures performed. We then constructed multivariable logistic regression models to identify factors associated with use of urgent surgical care. RESULTS: AIAN patients had lower mean age at surgery for all three surgeries compared with NHW patients. AIAN patients were at higher risk for urgent surgery for hip replacements (OR = 1.49, 95% CI 1.19-1.88), spinal fusions (OR = 1.39, 95% CI 1.04-1.87), and aortic valve replacements (OR = 2.06, 95% CI 1.12-3.80). CONCLUSION: AIAN patients were more likely to undergo urgent hip replacement, spinal fusion, and aortic valve replacement than NHW patients. AIAN patients underwent urgent surgery at younger ages. Medicaid insurance conferred higher risks for urgent surgery across all surgeries studied. Further research is warranted to more clearly identify the factors contributing to disparities among AIAN patients undergoing urgent surgery.

Power spectra reveal distinct BOLD resting-state time courses in white matter.

Accurate characterization of the time courses of blood-oxygen-level-dependent (BOLD) signal changes is crucial for the analysis and interpretation of functional MRI data. While several studies have shown that white matter (WM) exhibits distinct BOLD responses evoked by tasks, there have been no comprehensive investigations into the time courses of spontaneous signal fluctuations in WM. We measured the power spectra of the resting-state time courses in a set of regions within WM identified as showing synchronous signals using independent components analysis. In each component, a clear separation between voxels into two categories was evident, based on their power spectra: one group exhibited a single peak, and the other had an additional peak at a higher frequency. Their groupings are location specific, and their distributions reflect unique neurovascular and anatomical configurations. Importantly, the two categories of voxels differed in their engagement in functional integration, revealed by differences in the number of interregional connections based on the two categories separately. Taken together, these findings suggest WM signals are heterogeneous in nature and depend on local structural-vascular-functional associations.

Differential Recovery of Submodality Touch Neurons and Interareal Communication in Sensory Input-Deprived Area 3b and S2 Cortices.

Cortical reactivation and regain of interareal functional connections have been linked to the recovery of hand grasping behavior after loss of sensory inputs in primates. We investigated contributions of neurons in two hierarchically organized somatosensory areas, 3b and S2, by characterizing local field potential (LFP) and multiunit spiking activity in five states (rest, stimulus-on, sustained, stimulus-off, and induced) and interareal communication after grasping behavior of dorsal column lesioned male squirrel monkeys had mostly recovered. Compared with normal cortex, fMRI, LFP, and spiking response magnitudes to step indentations were significantly weaker. The sustained component of the spiking recovered much better than the stimulus-off response. Correlation between overall spiking and γ LFP remained strong within each recovered areas 3b and S2. The interareal correlations of γ LFP were severely disrupted, except in the resting and stimulus-on periods. Interareal correlation of spiking was disrupted in the stimulus-off period only. In summary, submodality of low threshold mechanoreceptive neurons recovered differentially in input-deprived area 3b and S2 when impaired global hand grasping behavior returned. Slow-adapting-like neurons recovered, whereas rapid-adapting-like neurons did not. Interareal communications were also severely compromised. We propose that slow-adapting-like neurons and afferents in recovered area 3b and S2 mediate recovery of impaired grasping behavior after dorsal column tract lesion.SIGNIFICANCE STATEMENT Sensory feedback is essential for execution of hand grasping behavior in primates. Reactivations of somatosensory cortices have been attributed to recovery of such behavior after loss of sensory inputs via largely unknown mechanisms. In input-deprived area 3b and S2 cortex, after hand grasping behavior mostly recovered, we found slow-adapting-like neurons were greatly recovered, whereas rapid-adapting-like neurons did not. Communications between area 3b and S2 neurons were severely compromised. We suggest that recovery of slow-adapting-like neurons in input-deprived area 3b and S2 may mediate the recovery of hand grasping behavior.

Functional alterations in bipartite network of white and grey matters during aging.

The effects of normal aging on functional connectivity (FC) within various brain networks of gray matter (GM) have been well-documented. However, the age effects on the networks of FC between white matter (WM) and GM, namely WM-GM FC, remains unclear. Evaluating crucial properties, such as global efficiency (GE), for a WM-GM FC network poses a challenge due to the absence of closed triangle paths which are essential for assessing network properties in traditional graph models. In this study, we propose a bipartite graph model to characterize the WM-GM FC network and quantify these challenging network properties. Leveraging this model, we assessed the WM-GM FC network properties at multiple scales across 1,462 cognitively normal subjects aged 22-96 years from three repositories (ADNI, BLSA and OASIS-3) and investigated the age effects on these properties throughout adulthood and during late adulthood (age ≥70 years). Our findings reveal that (1) heterogeneous alterations occurred in region-specific WM-GM FC over the adulthood and decline predominated during late adulthood; (2) the FC density of WM bundles engaged in memory, executive function and processing speed declined with age over adulthood, particularly in later years; and (3) the GE of attention, default, somatomotor, frontoparietal and limbic networks reduced with age over adulthood, and GE of visual network declined during late adulthood. These findings provide unpresented insights into multi-scale alterations in networks of WM-GM functional synchronizations during normal aging. Furthermore, our bipartite graph model offers an extendable framework for quantifying WM-engaged networks, which may contribute to a wide range of neuroscience research.

Racial inequities in the quality of surgical care among Medicare beneficiaries with localized prostate cancer.

BACKGROUND: US Black men are twice as likely to die from prostate cancer as men of other races. Lower quality care may contribute to this higher death rate. METHODS: Sociodemographic and clinical data were obtained for men in Surveillance, Epidemiology, and End Results-Medicare diagnosed with clinically localized prostate cancer (cT1-4N0/xM0/x) and managed primarily by radical prostatectomy (2005-2015). Surgical volume was determined for facility and surgeon. Relationships between race, surgeon and/or facility volume, and characteristics of treating facility with survival (all-cause and cancer-specific) were assessed using multivariable Cox regression and competing risk analysis. RESULTS: Black men represented 6.7% (n = 2123) of 31,478 cohort. They were younger at diagnosis, had longer time from diagnosis to surgery, lower socioeconomic status, higher prostate-specific antigen (PSA), and higher comorbid status compared with men of other races (p < .001). They were less likely to receive care from a surgeon or facility in the top volume percentile (p < .001); less likely to receive surgical care at a National Cancer Institute-designated cancer center and more likely seen at a minority-serving hospital; and less likely to travel ≥50 miles for surgical care. On multivariable analysis stratified by surgical volume, Black men receiving care from a surgeon or facility with lower volumes demonstrated increased risk of prostate cancer mortality (hazard ratio, 1.61; 95% confidence interval, 1.01-2.69) adjusting for age, clinical stage, PSA, and comorbidity index. CONCLUSIONS: Black Medicare beneficiaries with prostate cancer more commonly receive care from surgeons and facilities with lower volumes, likely affecting surgical quality and outcomes. Access to high-quality prostate cancer care may reduce racial inequities in disease outcomes, even among insured men. PLAIN LANGUAGE SUMMARY: Black men are twice as likely to die of prostate cancer than other US men. Lower quality care may contribute to higher rates of prostate cancer death. We used surgical volume to evaluate the relationship between race and quality of care. Black Medicare beneficiaries with prostate cancer more commonly received care from surgeons and facilities with lower volumes, correlating with a higher risk of prostate cancer death and indicating scarce resources for care. Access to high-quality prostate cancer care eases disparities in disease outcomes. Patient-centered interventions that increase access to high-quality care for Black men with prostate cancer are needed.

Patient-centered outcomes of telehealth for the care of rural-residing patients with urologic cancer.

BACKGROUND: Patients residing in rural areas with urologic cancers confront significant obstacles in obtaining oncologic care. In the Pacific Northwest, a sizeable portion of the population lives in a rural county. Telehealth offers a potential access solution. METHODS: Patients receiving urologic care through telehealth or an in-person appointment at the Fred Hutchinson Cancer Center in Seattle, Washington, were surveyed to assess appointment-related satisfaction and travel costs. Patients' residences were classified as rural or urban based on their self-reported ZIP code. Median patient satisfaction scores and appointment-related travel costs were compared by rural versus urban residence within telehealth and in-person appointment groups using Wilcoxon signed-rank or χ2 testing. RESULTS: A total of 1091 patients seen for urologic cancer care between June 2019 and April 2022 were included, 28.7% of which resided in a rural county. Patients were mostly non-Hispanic White (75%) and covered by Medicare (58%). Among rural-residing patients, telehealth and in-person appointment groups had the same median satisfaction score (61; interquartile ratio, 58, 63). More rural-residing than urban-residing patients in the telehealth appointment groups strongly agreed that "Considering the cost and time commitment of my appointment, I would choose to meet with my provider in this setting in the future" (67% vs. 58%, p = .03). Rural-residing patients with in-person appointments carried a higher financial burden than those with telehealth appointments (medians, $80 vs. $0; p <.001). CONCLUSIONS: Appointment-related costs are high among rural-residing patients traveling for urologic oncologic care. Telehealth provides an affordable solution that does not compromise patient satisfaction.

Multi-pilot implementation experiences of patient-centered pathology reports: lessons learned for the advancement of patient-centered tools for cancer decision-making.

PURPOSE: New federal legislation in the United States grants patients expanded access to their medical records, making it critical that medical records information is understandable to patients. Provision of informational summaries significantly increase patient perceptions of patient-centered care and reduce feelings of uncertainty, yet their use for cancer pathology is limited. METHODS: Our team developed and piloted patient-centered versions of pathology reports (PCPRs) for four cancer organ sites: prostate, bladder, breast, and colorectal polyp. The objective of this analysis was to identify common barriers and facilitators to support dissemination of PCPRs in care delivery settings. We analyzed quantitative and qualitative data from pilot PCPR implementations, guided by the RE-AIM framework to explore constructs of reach, effectiveness, adoption, implementation, and maintenance. RESULTS: We present two case studies of PCPR implementation - breast cancer and colorectal polyps-that showcase diverse workflows for pathology reporting. Cross-pilot learnings emphasize the potential for PCPRs to improve patient satisfaction, knowledge, quality of shared decision-making activities, yet several barriers to dissemination exist. CONCLUSION: While there is promise in expanding patient-centered cancer communication tools, more work is needed to expand the technological capacity for PCPRs and connect PCPRs to opportunities to reduce costs, improve quality, and reduce waste in care delivery systems.

Diffusion time dependency of extracellular diffusion.

PURPOSE: To quantify the variations of the power-law dependences on diffusion time t or gradient frequency f $$ f $$ of extracellular water diffusion measured by diffusion MRI (dMRI). METHODS: Model cellular systems containing only extracellular water were used to investigate the t / f $$ t/f $$ dependence of D ex $$ {D}_{ex} $$ , the extracellular diffusion coefficient. Computer simulations used a randomly packed tissue model with realistic intracellular volume fractions and cell sizes. DMRI measurements were performed on samples consisting of liposomes containing heavy water(D2 O, deuterium oxide) dispersed in regular water (H2 O). D ex $$ {D}_{ex} $$ was obtained over a broad t $$ t $$ range (∼1-1000 ms) and then fit power-law equations D ex ( t ) = D const + const · t - ϑ t $$ {D}_{ex}(t)={D}_{\mathrm{const}}+\mathrm{const}\cdotp {t}^{-{\vartheta}_t} $$ and D ex ( f ) = D const + const · f ϑ f $$ {D}_{ex}(f)={D}_{\mathrm{const}}+\mathrm{const}\cdotp {f}^{\vartheta_f} $$ . RESULTS: Both simulated and experimental results suggest that no single power-law adequately describes the behavior of D ex $$ {D}_{ex} $$ over the range of diffusion times of most interest in practical dMRI. Previous theoretical predictions are accurate over only limited t $$ t $$ ranges; for example, θ t = θ f = - 1 2 $$ {\theta}_t={\theta}_f=-\frac{1}{2} $$ is valid only for short times, whereas θ t = 1 $$ {\theta}_t=1 $$ or θ f = 3 2 $$ {\theta}_f=\frac{3}{2} $$ is valid only for long times but cannot describe other ranges simultaneously. For the specific t $$ t $$ range of 5-70 ms used in typical human dMRI measurements, θ t = θ f = 1 $$ {\theta}_t={\theta}_f=1 $$ matches the data well empirically. CONCLUSION: The optimal power-law fit of extracellular diffusion varies with diffusion time. The dependency obtained at short or long t $$ t $$ limits cannot be applied to typical dMRI measurements in human cancer or liver. It is essential to determine the appropriate diffusion time range when modeling extracellular diffusion in dMRI-based quantitative microstructural imaging.

Detection of laser-associated heating in the brain during simultaneous fMRI and optogenetic stimulation.

PURPOSE: To calculate temperatures from T2 *-weighted images collected during optogenetic fMRI based on proton resonance frequency (PRF) shift thermometry, to monitor confounding heating effects and determine appropriate light parameters for optogenetic stimulation. METHODS: fMRI is mainly based on long-TE gradient-recalled echo acquisitions that are also suitable for measuring small temperature changes via the PRF shift. A motion- and respiration-robust processing pipeline was developed to calculate temperature changes based on the PRF shift directly from the T2 *-weighted images collected for fMRI with a two-shot 2D gradient-recalled echo-EPI sequence at 9.4T. Optogenetic fMRI protocols which differed in stimulation durations (3, 6 and 9 s) within a total block duration of 30 s were applied in a squirrel monkey to validate the methods with blue and green light (20 Hz, 30 mW) delivery interleaved between periods. General linear modeling was performed on the resulting time series temperature maps to verify if light delivery with each protocol resulted in significant heating in the brain around the optical fiber. RESULTS: The temperature SD was 0.05°C with the proposed imaging protocol and processing. Statistical analysis showed that the optogenetic stimulation protocol with a 3 s stimulation duration did not result in significant temperature rises. Significant temperature rises up to 0.13°C (p < 0. 05) were observed with 6 and 9 s stimulation durations for blue and green light. CONCLUSION: The proposed processing pipeline can be useful for the design of optogenetic stimulation protocols and for monitoring confounding heating effects.

J-Difference editing (MEGA) of lactate in the human brain at 3T.

PURPOSE: The need to detect and quantify brain lactate accurately by MRS has stimulated the development of editing sequences based on J coupling effects. In J-difference editing of lactate, threonine can be co-edited and it contaminates lactate estimates due to the spectral proximity of the coupling partners of their methyl protons. We therefore implemented narrow-band editing 180° pulses (E180) in MEGA-PRESS acquisitions to resolve separately the 1.3-ppm resonances of lactate and threonine. METHODS: Two 45.3-ms rectangular E180 pulses, which had negligible effects 0.15-ppm away from the carrier frequency, were implemented in a MEGA-PRESS sequence with TE 139 ms. Three acquisitions were designed to selectively edit lactate and threonine, in which the E180 pulses were tuned to 4.1 ppm, 4.25 ppm, and a frequency far off resonance. Editing performance was validated with numerical analyses and acquisitions from phantoms. The narrow-band E180 MEGA and another MEGA-PRESS sequence with broad-band E180 pulses were evaluated in six healthy subjects. RESULTS: The 45.3-ms E180 MEGA offered a difference-edited lactate signal with lower intensity and reduced contamination from threonine compared to the broad-band E180 MEGA. The 45.3 ms E180 pulse had MEGA editing effects over a frequency range larger than seen in the singlet-resonance inversion profile. Lactate and threonine in healthy brain were both estimated to be 0.4 ± 0.1 mM, with reference to N-acetylaspartate at 12 mM. CONCLUSION: Narrow-band E180 MEGA editing minimizes threonine contamination of lactate spectra and may improve the ability to detect modest changes in lactate levels.

Severity of polycystic kidney disease revealed by multiparametric MRI.

PURPOSE: We aimed to compare multiple MRI parameters, including relaxation rates ( R 1 $$ {R}_1 $$ , R 2 $$ {R}_2 $$ , and R 1 ρ $$ {R}_{1\rho } $$ ), ADC from diffusion weighted imaging, pool size ratio (PSR) from quantitative magnetization transfer, and measures of exchange from spin-lock imaging ( S ρ $$ {S}_{\rho } $$ ), for assessing and predicting the severity of polycystic kidney disease (PKD) over time. METHODS: Pcy/Pcy mice with CD1 strain, a mouse model of autosomal dominant PKD, were imaged at 5, 9, and 26 wk of age using a 7T MRI system. Twelve-week normal CD1 mice were used as controls. Post-mortem paraffin tissue sections were stained using hematoxylin and eosin and picrosirius red to identify histological changes. RESULTS: Histology detected segmental cyst formation in the early stage (week 5) and progression of PKD over time in Pcy kidneys. In T 2 $$ {T}_2 $$ -weighted images, small cysts appeared locally in cystic kidneys in week 5 and gradually extended to the whole cortex and outer stripe of outer medulla region from week 5 to week 26. Regional PSR, R 1 $$ {R}_1 $$ , R 2 $$ {R}_2 $$ , and R 1 ρ $$ {R}_{1\rho } $$ decreased consistently over time compared to normal kidneys, with significant changes detected in week 5. Among all the MRI measures, R 2 $$ {R}_2 $$ and R 1 ρ $$ {R}_{1\rho } $$ allow highest detectability to PKD, while PSR and R 1 $$ {R}_1 $$ have highest correlation with pathological indices of PKD. Using optimum MRI parameters as regressors, multiple linear regression provides reliable prediction of PKD progression. CONCLUSION: R 2 $$ {R}_2 $$ , R 1 $$ {R}_1 $$ , and PSR are sensitive indicators of the presence of PKD. Multiparametric MRI allows a comprehensive analysis of renal changes caused by cyst formation and expansion.

Correction of errors in estimates of T1ρ at low spin-lock amplitudes in the presence of B0 and B1 inhomogeneities.

Relaxation rates R1ρ in the rotating frame measured by spin-lock methods at very low locking amplitudes (≤ 100 Hz) are sensitive to the effects of water diffusion in intrinsic gradients and may provide information on tissue microvasculature, but accurate estimates are challenging in the presence of B0 and B1 inhomogeneities. Although composite pulse preparations have been developed to compensate for nonuniform fields, the transverse magnetization comprises different components and the spin-lock signals measured do not decay exponentially as a function of locking interval at low locking amplitudes. For example, during a typical preparation sequence, some of the magnetization in the transverse plane is nutated to the Z-axis and later tipped back, and so does not experience R1ρ relaxation. As a result, if the spin-lock signals are fit to a monoexponential decay with locking interval, there are residual errors in quantitative estimates of relaxation rates R1ρ and their dispersion with weak locking fields. We developed an approximate theoretical analysis to model the behaviors of the different components of the magnetization, which provides a means to correct these errors. The performance of this correction approach was evaluated both through numerical simulations and on human brain images at 3 T, and compared with a previous correction method using matrix multiplication. Our correction approach has better performance than the previous method at low locking amplitudes. Through careful shimming, the correction approach can be applied in studies using low spin-lock amplitudes to assess the contribution of diffusion to R1ρ dispersion and to derive estimates of microvascular sizes and spacings. The results of imaging eight healthy subjects suggest that R1ρ dispersion in human brain at low locking fields arises from diffusion among inhomogeneities that generate intrinsic gradients on a scale of capillaries (~7.4 ± 0.5 µm).

Protocol of the Comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) study: a pragmatic, prospective multicenter observational cohort study of recurrent high-grade non-muscle invasive bladder cancer.

BACKGROUND: Bladder cancer poses a significant public health burden, with high recurrence and progression rates in patients with non-muscle-invasive bladder cancer (NMIBC). Current treatment options include bladder-sparing therapies (BST) and radical cystectomy, both with associated risks and benefits. However, evidence supporting optimal management decisions for patients with recurrent high-grade NMIBC remains limited, leading to uncertainty for patients and clinicians. The CISTO (Comparison of Intravesical Therapy and Surgery as Treatment Options) Study aims to address this critical knowledge gap by comparing outcomes between patients undergoing BST and radical cystectomy. METHODS: The CISTO Study is a pragmatic, prospective observational cohort trial across 36 academic and community urology practices in the US. The study will enroll 572 patients with a diagnosis of recurrent high-grade NMIBC who select management with either BST or radical cystectomy. The primary outcome is health-related quality of life (QOL) at 12 months as measured with the EORTC-QLQ-C30. Secondary outcomes include bladder cancer-specific QOL, progression-free survival, cancer-specific survival, and financial toxicity. The study will also assess patient preferences for treatment outcomes. Statistical analyses will employ targeted maximum likelihood estimation (TMLE) to address treatment selection bias and confounding by indication. DISCUSSION: The CISTO Study is powered to detect clinically important differences in QOL and cancer-specific survival between the two treatment approaches. By including a diverse patient population, the study also aims to assess outcomes across the following patient characteristics: age, gender, race, burden of comorbid health conditions, cancer severity, caregiver status, social determinants of health, and rurality. Treatment outcomes may also vary by patient preferences, health literacy, and baseline QOL. The CISTO Study will fill a crucial evidence gap in the management of recurrent high-grade NMIBC, providing evidence-based guidance for patients and clinicians in choosing between BST and radical cystectomy. The CISTO study will provide an evidence-based approach to identifying the right treatment for the right patient at the right time in the challenging clinical setting of recurrent high-grade NMIBC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03933826. Registered on May 1, 2019.