Faculty Bibliography

PURPOSE/OBJECTIVE:This study evaluated the extent of prostate displacement during SBRT on an MRI Linac using comprehensive motion management (CMM) and identified variables associated with intrafraction motion (IFM). METHODS:212 patients with clinically localized prostate cancer were treated with 5-fraction SBRT on a 1.5 T MR-Linac where IFM was continuously tracked and gated by CMM. Pre-beam positional shifts were identified from MRI registration prior to beam delivery. Intrafraction positional variability during beam delivery was evaluated, and multivariable analysis identified variables associated with IFM. RESULTS:In 614 fractions (62.7%), a > 1.5 mm pre-beam positional shift led to an adapt-to-position (ATP) plan correction. Mean anterior-posterior and superior-inferior pre-beam shifts were 2.2 mm and 2.1 mm, respectively. For 962 evaluable fractions, the median beam-on-time was 13.7 min with a mean duty cycle of 95.8%. Sustained > 3 mm displacement was observed in 520 fractions (54.1%) with a median cumulative duration of 24 s; >5 mm displacement was observed in 209 fractions (21.7%) with a median duration of 12.4 s. The ATS + ATP workflow was associated with reduced odds of sustained > 3 mm motion (p = 0.035), while older age was associated with increased odds (p = 0.011). CONCLUSIONS:Significant prostate shifts can occur immediately prior to and during radiation beam delivery, frequently exceeding applied margins and potentially leading to tumor underdosage. Continuous motion tracking and gating during prostate SBRT is an important tool in reducing IFM and enhance treatment delivery accuracy.

PURPOSE OF THE REPORT/OBJECTIVE:To determine the prevalence, etiology, and clinical significance of incidental focal small bowel FDG uptake in patients undergoing PET/CT for staging of non-small bowel cancers. MATERIAL AND METHODS/METHODS:Retrospective review of consecutive FDG PET/CT examinations obtained for cancer staging with incidental focal small bowel radiotracer uptake was performed. Exclusion criteria included known small bowel pathology or insufficient reference standard. Imaging findings assessed included lesion location, number, CT correlate, SUVmax, and presence of metastases outside the bowel. Clinical data included age, sex, cancer clinical setting, origin, and stage. Focal small bowel FDG uptake etiology (benign vs. metastatic) was determined by composite reference standard (histopathology, clinical, and imaging follow-up). Statistical analyses included Wilcoxon rank-sum test, Pearson's χ2 test, Fisher exact test, and ROC curve analyses. RESULTS:In a review of 147,516 PET/CT examinations, incidental focal small bowel FDG uptake was rare, with a prevalence of 0.1% (88/147,516). Most cases were metastatic, 60.2% (53/88), most commonly spread from lymphoma [32.1% (17/53)] and melanoma [30.2% (16/53)]. Metastatic lesions were evenly distributed throughout the ileum [47.2% (25/53)] and jejunum [39.6% (21/53)]. Metastatic focal small bowel FDG uptake was associated with presence of other sites of distant metastases, higher SUVmax, and presence of a CT correlate (P <0.01). CONCLUSIONS:Incidental focal small bowel FDG uptake is rare. Most small bowel hypermetabolic foci are metastatic and are predominantly encountered with melanoma and lymphoma. Multiple imaging and clinical factors helped differentiate between benign and metastatic focal small bowel FDG uptake.

BACKGROUND:Feeding problems affect many children, yet their connection with diet quality in later childhood is unknown, despite the important role of diet quality on health outcomes, such as obesity. OBJECTIVE:To examine feeding problem behaviors and diet quality in later childhood. DESIGN/METHODS:The frequency of problematic feeding behaviors (i.e., items related to food refusal, feeding difficulties, and distress) were parent-reported at 18 and 24 months in a birth cohort (2008-2010) from New York state (n = 4,989). In this previously validated feeding behaviors scale, parents responded to how often their child engaged in behaviors such as crying/screaming during meals and food refusal, to create an average feeding problems score. Typical daily servings of food items that a child consumed were parent-reported at 30 months, 36 months, 7 years, and 9 years and diet quality using the Youth Healthy Eating Index (YHEI) was calculated, with a higher score indicating better diet quality. Mixed effects analyses calculated mean differences in YHEI per unit increase in feeding problem scores, adjusting for sociodemographic and health-related factors, such as parental education, gestational age, and any breastfeeding duration. RESULTS:Feeding problem scores at 18 and 24 months were prospectively associated with lower YHEI scores at 30/36 months (18 months: B = -1.10, 95% CI: -1.93, -0.27; 24 months: B = -1.56, 95% CI: -2.33, -0.79). Similar associations were observed at 7/9 years (18 months: B = -1.30, 95% CI: -2.61, 0.00; 24 months: B = -1.65, 95% CI: -2.96, -0.34). CONCLUSIONS:Higher feeding problems in infancy (18 and 24 months) were associated with lower quality diets in childhood, even after children started school. These findings highlight the importance of feeding behaviors to long-term diet quality even with observations as early as 18 months. TRIAL REGISTRATION/BACKGROUND:NCT03106493 in clinicaltrials.gov (Dates: 07/2008-11/2019, Study Registration Date: 2017-04-10).

CONTEXT/BACKGROUND:Temozolomide (TMZ) can be an effective medical treatment for aggressive pituitary tumors. In case of disease recurrence following TMZ treatment, however, treatment with the drug generally does not control tumor regrowth. OBJECTIVE:This work aimed to better understand the mechanisms of resistance of corticotroph tumors to TMZ in the context of heterogeneity of methylguanine-DNA methyltransferase (MGMT) expression. METHODS:We performed immunohistochemical analysis of the MGMT expression pattern in 25 corticotroph tumors to evaluate intratumoral heterogeneity. In addition, we created in vitro models of AtT20 corticotroph tumor cells with acquired TMZ-resistance after exposure to high- and low-dose TMZ, the latter representing a clinically achievable TMZ level. RESULTS:MGMT immunostaining in corticotroph tumors showed a considerable heterogeneous intertumoral and intratumoral distribution pattern in 80% of tumors. In the in vitro model, high- and low-dose TMZ challenges induced a 6.3- and 3.4-fold decreased sensitivity to the growth inhibitory effect of TMZ. TMZ-induced changes in cell cycle phases were lower in TMZ-resistant cells than in vehicle-challenged cells. TMZ-resistant cells had higher Mgmt messenger RNA and protein expression and 1.8-fold higher number of Mgmt-positive cells. No difference was observed in the level of Mgmt promoter methylation. CONCLUSION/CONCLUSIONS:Corticotroph pituitary tumors demonstrate a high intertumoral and intratumoral heterogeneity in MGMT expression. In an acquired TMZ-resistant corticotroph pituitary tumor cell model, TMZ resistance was associated with strong increase in MGMT expression and percentage of MGMT-positive cells. We hypothesize that clonal selection of high MGMT-expressing cells is involved in this acquired TMZ resistance.

The bone marrow niche (BMN) plays a central role in regulating hematopoietic stem-cell (HSC) maintenance, lineage commitment, and immune homeostasis, while also supporting osteogenesis and maintaining skeletal integrity. Once considered static, the BMN is now recognized as a dynamic and responsive microenvironment that integrates local signals and systemic cues to meet physiological demands and respond to stress. Aging causes profound and progressive changes to this niche, leading to functional decline across both hematopoietic and stromal compartments. Recent advances in high-resolution imaging, single-cell and spatial transcriptomics, and in vivo lineage tracing have revealed remarkable heterogeneity and plasticity within the vascular and mesenchymal elements of this niche. Yet, key questions remain unresolved, including the identity and hierarchy of mesenchymal and osteolineage cells, the specialization of subsets of endothelial cells, the integration of systemic regulation, and whether the aging bone marrow acts as a driver or a passenger in malignancy and chronic inflammation. This review revisits current models of the BMN, with a focus on the reciprocal interactions between osteogenic cells and specialized vasculature, and how their disruption during aging impairs hematopoietic output and skeletal remodeling. We also examine how systemic factors such as neural input, metabolic status, and inflammatory signaling influence the aging of the BMN. Finally, we highlight emerging translational platforms, including iPSC-derived bone marrow organoids, engineered niches/hydrogels, and vascularized organ-on-chip systems, that enable mechanistic testing of rejuvenation strategies. Together, these insights have the potential to pave the way toward targeted interventions that restore the function of the BMN and promote healthy aging of the bone and blood systems.

PURPOSE/OBJECTIVE:To develop a novel single-shot radial echo planar imaging (ss-rEPI) technique for rapid, distortion-free brain imaging in functional MRI experiments. METHODS:* mapping and QSM. Visual BOLD fMRI experiments were conducted and evaluated against Cartesian EPI measurements. RESULTS:* measurements. CONCLUSION/CONCLUSIONS:modeling is critical for ss-rEPI performance. Advanced reconstruction techniques and self-calibration methods could further enhance its speed, performance, and applicability across diverse MRI techniques.