Evaluation of superficial xenograft volume estimation by ultrasound and caliper against MRI in a longitudinal pre-clinical radiotherapeutic setting.

BACKGROUND: Accurate tumor volume estimation is important for evaluating the response to radionuclide therapy and external beam radiotherapy as well as to other pharmaceuticals. A common method for monitoring the growth of subcutaneous tumors in pre-clinical models and assessing the treatment response is to measure the tumor length and width by external calipers to estimate its volume. This procedure relies on an assumption of a spheroidal tumor shape wherein the tumor depth equals the width and can yield considerably inaccuracies. Ultrasound imaging is a non-invasive technique that can measure all three axes of the tumor and might be an alternative to caliper measurement with potentially greater accuracy and comparable ease-of-use and throughput. Both 2D and 3D ultrasound imaging are possible, the former offering short scan times without the need for anesthesia and heating-valuable factors for longitudinal studies in large animal cohorts. Nevertheless, tumor volume estimation accuracy by 2D ultrasound imaging has seen limited investigation. In this study we have evaluated the accuracy of tumor volume estimation by caliper and 2D ultrasound with comparisons to reference measurements by magnetic resonance imaging (MRI) in a pre-clinical model of prostate cancer treated with either external beam radiotherapy, radionuclide therapy, or no treatment. RESULTS: Tumor volumes were measured longitudinally in 29 mice by caliper, ultrasound, and MRI before and after external beam radiotherapy, [177Lu]Lu-PSMA-617 radionuclide therapy, or no treatment. Caliper measurements had a marked bias, overestimating the tumor volumes by a median of 150% compared to MRI. Ultrasound measurements were markedly more accurate, with a median bias of -21% compared to MRI. CONCLUSION: Ultrasound imaging is a reliable and accurate method for tumor volume estimation in pre-clinical models of radiotherapy, whereas caliper measurements are prone to overestimation.

Size and Surface Properties of Functionalized Organosilica Particles Impact Cell-Particle Interactions Including Mitochondrial Activity.

Understanding of the interactions between macrophages and multifunctional nanoparticles is important for development of novel macrophage-based immunotherapies. Here, we investigated the effects of fluorescent thiol-organosilica particle size and surface properties on cell-particle interactions, including mitochondrial activity, using the mouse macrophage cell line J774A.1. Three different sizes of thiol-organosilica particles (150, 400, and 680 nm in diameter) containing fluorescein (OS/F150, OS/F400, and OS/F680) and particles surface functionalized with polyethylenimine (PEI) (OS/F150PEI, OS/F400PEI, and OS/F680PEI) were prepared. Flow cytometric analysis, time-lapse imaging, and single-cell analysis of particle uptake and mitochondrial activity of J774A.1 cells demonstrated variations in uptake and kinetics depending on the particle size and surface as well as on each individual cell. Cells treated with OS/F150 and OS/F150PEI showed higher uptake and mitochondrial activity than those treated with other particles. The interaction between endosomes and mitochondria was observed using 3D fluorescent imaging and was characterized by the involvement of iron transport into mitochondria by iron-containing proteins adsorbed on the particle surface. Scanning electron microscopy of the cells treated with the particles revealed alterations in cell membrane morphology, depending on particle size and surface. We performed correlative light and electron microscopy combined with time-lapse and 3D imaging to develop an integrated correlation analysis of particle uptake, mitochondrial activity, and cell membrane morphology in single macrophages. These cell-specific characteristics of macrophages against functional particles and their evaluation methods are crucial for understanding the immunological functions of individual macrophages and developing novel immunotherapies.

Relationship Between Absorbed Dose and Response in Neuroendocrine Tumors Treated with [177Lu]Lu-DOTATATE.

Peptide receptor radionuclide therapy presents the possibility of tracing and quantifying the uptake of the drug in the body and performing dosimetry, potentially allowing individualization of treatment schemes. However, the details of how neuroendocrine tumors (NETs) respond to different absorbed doses are insufficiently known. Here, we investigated the relationship between tumor-absorbed dose and tumor response in a cohort of patients with NETs treated with [177Lu]Lu-DOTATATE. Methods: This was a retrospective study based on 69 tumors in 32 patients treated within a clinical trial. Dosimetry was performed at each cycle of [177Lu]Lu-DOTATATE, rendering 366 individual absorbed dose assessments. Hybrid planar-SPECT/CT imaging using [177Lu]Lu-DOTATATE was used, including quantitative SPECT reconstruction, voxel-based absorbed dose rate calculation, semiautomatic image segmentation, and partial-volume correction. Changes in tumor volume were used to determine tumor response. The volume for each tumor was manually delineated on consecutive CT scans, giving a total of 712 individual tumor volume assessments. Tumors were stratified according to grade. The relationship between absorbed dose and response was investigated using mixed-effects models and logistic regression. Tumors smaller than 4 cm3 were excluded. Results: In grade 2 NETs, a clear relationship between absorbed dose and volume reduction was observed. Our observations suggest a 90% probability of partial tumor response for an accumulated tumor-absorbed dose of at least 135 Gy. Conclusion: Our findings are in accordance with previous observations regarding the relationship between tumor shrinkage and absorbed dose. Moreover, our data suggest an absorbed dose threshold for partial response in grade 2 NETs. These observations provide valuable insights for the design of dosimetry-guided peptide receptor radionuclide therapy schemes.

Neural digital twins: reconstructing complex medical environments for spatial planning in virtual reality.

PURPOSE: Specialized robotic and surgical tools are increasing the complexity of operating rooms (ORs), requiring elaborate preparation especially when techniques or devices are to be used for the first time. Spatial planning can improve efficiency and identify procedural obstacles ahead of time, but real ORs offer little availability to optimize space utilization. Methods for creating reconstructions of physical setups, i.e., digital twins, are needed to enable immersive spatial planning of such complex environments in virtual reality. METHODS: We present a neural rendering-based method to create immersive digital twins of complex medical environments and devices from casual video capture that enables spatial planning of surgical scenarios. To evaluate our approach we recreate two operating rooms and ten objects through neural reconstruction, then conduct a user study with 21 graduate students carrying out planning tasks in the resulting virtual environment. We analyze task load, presence, perceived utility, plus exploration and interaction behavior compared to low visual complexity versions of the same environments. RESULTS: Results show significantly increased perceived utility and presence using the neural reconstruction-based environments, combined with higher perceived workload and exploratory behavior. There's no significant difference in interactivity. CONCLUSION: We explore the feasibility of using modern reconstruction techniques to create digital twins of complex medical environments and objects. Without requiring expert knowledge or specialized hardware, users can create, explore and interact with objects in virtual environments. Results indicate benefits like high perceived utility while being technically approachable, which may indicate promise of this approach for spatial planning and beyond.

Ocular, Visual, and Anatomical Outcomes in Eyes Requiring Incisional Intraocular Pressure-Lowering Surgery Following the 0.19-mg Fluocinolone Acetonide Intravitreal Implant.

BACKGROUND AND OBJECTIVE: To assess ocular, visual, and anatomical outcomes following the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN®) and incisional intraocular pressure (IOP)-lowering surgery in diabetic macular edema. PATIENTS AND METHODS: From a 36-month, phase 4, open-label, observational study (N = 202 eyes, 159 patients), 8 eyes (7 patients) required IOP-lowering surgery post-FAc; eyes were segregated by FAc-induced (n = 5, 2.47%) versus neovascular glaucoma (NVG)-related (n = 3, 1.49%) IOP elevations and assessed for IOP, best corrected visual acuity (BCVA), central subfield thickness (CST), and cup-to-disc ratio (c/d). RESULTS: Changes at 36 months were +5.4 letters BCVA (P > 0.05) and +0.09 c/d (P = 0.0217); IOP and CST were unchanged. FAc-induced-group eyes required fewer IOP-lowering medications than NVG-group eyes (2.0 versus 4.0; P < 0.01) but for longer duration (15.2 versus 2.6 months; P < 0.001). CONCLUSIONS: Post-FAc IOP-lowering surgery, regardless of cause, largely did not affect the outcomes measured; these procedures, then, may not meaningfully threaten positive outcomes. [Ophthalmic Surg Lasers Imaging Retina 2024;55:22-29.].

Feasibility of 177Lu activity quantification using a small portable CZT-based gamma-camera.

BACKGROUND: In image processing for activity quantification, the end goal is to produce a metric that is independent of the measurement geometry. Photon attenuation needs to be accounted for and can be accomplished utilizing spectral information, avoiding the need of additional image acquisitions. The aim of this work is to investigate the feasibility of 177Lu activity quantification with a small CZT-based hand-held gamma-camera, using such an attenuation correction method. METHODS: A previously presented dual photopeak method, based on the differential attenuation for two photon energies, is adapted for the three photopeaks at 55 keV, 113 keV, and 208 keV for 177Lu. The measurement model describes the count rates in each energy window as a function of source depth and activity, accounting for distance-dependent system sensitivity, attenuation, and build-up. Parameter values are estimated from characterizing measurements, and the source depth and activity are obtained by minimizing the difference between measured and modelled count rates. The method is applied and evaluated in phantom measurements, in a clinical setting for superficial lesions in two patients, and in a pre-clinical setting for one human tumour xenograft. Evaluation is made for a LEHR and an MEGP collimator. RESULTS: For phantom measurements at clinically relevant depths, the average (and standard deviation) in activity errors are 17% ± 9.6% (LEHR) and 2.9% ± 3.6% (MEGP). For patient measurements, deviations from activity estimates from planar images from a full-sized gamma-camera are 0% ± 21% (LEHR) and 16% ± 18% (MEGP). For mouse measurements, average deviations of - 16% (LEHR) and - 6% (MEGP) are obtained when compared to a small-animal SPECT/CT system. The MEGP collimator appears to be better suited for activity quantification, yielding a smaller variability in activity estimates, whereas the LEHR results are more severely affected by septal penetration. CONCLUSIONS: Activity quantification for 177Lu using the hand-held camera is found to be feasible. The readily available nature of the hand-held camera may enable more frequent activity quantification in e.g., superficial structures in patients or in the pre-clinical setting.

Maternal prenatal, with or without postpartum, vitamin D3 supplementation does not improve maternal iron status at delivery or infant iron status at 6 months of age: secondary analysis of a randomised controlled trial.

Background: Vitamin D may modify iron status through regulation of hepcidin and inflammatory pathways. This study aimed to investigate effects of maternal vitamin D supplementation on iron status in pregnancy and early infancy. Methods: In a trial in Dhaka, Bangladesh, women (n=1300) were randomised to one of five vitamin D3 regimens from 17 to 24 weeks' gestation until 26 weeks postpartum (prenatal; postpartum doses): 0;0, 4200;0, 16 800;0, 28 000;0 or 28 000;28 000 IU/week. All participants received standard iron-folic acid supplementation. In this secondary analysis (n=998), we examined effects of prenatal;postpartum vitamin D on serum ferritin and other biomarkers of maternal iron status (transferrin saturation, total iron binding capacity, soluble transferrin receptor and hepcidin) at delivery, and infant ferritin and haemoglobin at 6 months of age. Using linear regression, we estimated per cent mean differences between each intervention group and placebo with 95% CIs, with and without adjustment for baseline ferritin or inflammatory biomarkers (C reactive protein and α-1-acid glycoprotein (AGP)). Results: At delivery, ferritin concentrations were similar between each intervention group and placebo in unadjusted (n=998) and baseline ferritin-adjusted analyses (n=992; p>0.05). Compared with placebo, AGP was lower in each intervention group (per cent difference (95% CI) = -11% (-21 to -1.0), -14% (-23 to -3.5) and -11% (-19 to -2.0) in the 4200 IU/week, 16 800 IU/week and 28 000 IU/week groups, respectively; n=779). In the subgroup of women with baseline 25-hydroxyvitamin D < 30 nmol/L, ferritin was lower in each intervention group versus placebo (-23% (-37 to -5.0), -20% (-35 to -1.9) and -20% (-33 to -4.1) in the 4200 IU/week, 16 800 IU/week and 28 000 IU/week groups, respectively; n=645); effects were slightly attenuated after adjustment for inflammation (n=510). There were no effects of vitamin D on other iron biomarkers among women at delivery or infants aged 6 months. Conclusion: These findings do not support improvement of iron status by vitamin D. The effect of prenatal vitamin D supplementation on ferritin may reflect an anti-inflammatory mechanism.