The Influence of Size on the Intracranial Distribution of Biomedical Nanoparticles Administered by Convection-enhanced Delivery in Minipigs.

Because of the blood-brain barrier (BBB), successful drug delivery to the brain has long been a key objective for the medical community, calling for pioneering technologies to overcome this challenge. Convection-enhanced delivery (CED), a form of direct intraparenchymal microinfusion, shows promise but requires optimal infusate design and real-time distribution monitoring. The size of the infused substances appears to be especially critical, with current knowledge being limited. Herein, we examined the intracranial administration of polyethylene glycol (PEG)-coated nanoparticles (NPs) of various sizes using CED in groups of healthy minipigs (n = 3). We employed stealth liposomes (LIPs, 130 nm) and two gold nanoparticle designs (AuNPs) of different diameters (8 and 40 nm). All were labeled with copper-64 for quantitative and real-time monitoring of the infusion via positron emission tomography (PET). NPs were infused via two catheters inserted bilaterally in the putaminal regions of the animals. Our results suggest CED with NPs holds promise for precise brain drug delivery, with larger LIPs exhibiting superior distribution volumes and intracranial retention over smaller AuNPs. PET imaging alongside CED enabled dynamic visualization of the process, target coverage, timely detection of suboptimal infusion, and quantification of distribution volumes and concentration gradients. These findings may augment the therapeutic efficacy of the delivery procedure while mitigating unwarranted side effects associated with nonvisually monitored delivery approaches. This is of vital importance, especially for chronic intermittent infusions through implanted catheters, as this information enables informed decisions for modulating targeted infusion volumes on a catheter-by-catheter, patient-by-patient basis.

Spatiotemporal Gait Parameters and Gait Asymmetry in Patients With Lumbar Disc Herniation, Treated With Microdiscectomy: A Prospective, Observational Study.

OBJECTIVE: The aim of this study was to emphasize on the interaction of spatial and temporal gait parameters and analyse the gait asymmetry in the patients with lumbar disc herniation (LDH) before and after microdiscectomy. METHODS: This was a prospective, observational study conducted on 59 cases of LDH planned for lumbar microdiscectomy, and healthy control group with 54 participants for analysis was performed prior to surgery and 15 days after surgery. The spatiotemporal gait parameters were measured using a "Win-Track" gait analysis platform system. All the participants walked barefoot for 10 times with their normal walking speed in the same day. The 3 flawless walking data were recorded and the arithmetic means were computed. The gait symmetry index was used to calculate the walking asymmetry. The pain intensity of the patients was recorded shortly before performing the analysis by a visual analogue scale. RESULTS: In the postoperative assessment LDH patients had significantly shorter temporal parameters, longer spatial parameters, faster walking speed, and more cadence than the preoperative assessment (p < 0.05). There were improvements in the asymmetry values of the postoperative gait parameters compared to the preoperative values, but these differences were not significant (p > 0.05). In addition, there was a significant difference in all parameters in terms of gait asymmetry between the postoperative assessment and the healthy controls (p < 0.05). CONCLUSION: These results can guide the patient-specific evaluating and implementation of gait rehabilitation programs, and design protocols before or after surgery in the LDH patients.

Investigating the attenuating effect of telmisartan against radiation-induced intestinal injury using 18F-FDG micro-PET imaging.

BACKGROUND AND OBJECTIVE: This study was aimed to investigate the ability of 18F-Fluro-deoxy-glucose (18F-FDG)-based micro-positron emission tomography (microPET) imaging to evaluate the efficacy of telmisartan, a highly selective angiotensin II receptor antagonist (ARA), in intestinal tissue recovery process after in vivo irradiation. METHODS: Male Balb/c mice were randomly divided into four groups of control, telmisartan, irradiation, and telmisartan + irradiation. A solution of telmisartan in phosphate-buffered saline (PBS) was administered orally at 12 mg/kg body weight for seven consecutive days prior to whole body exposing to a single sub-lethal dose of 5 Gy X-rays. The mice were imaged using 18F-FDG microPET at 9 and 30 days post-irradiation. The 18F-FDG uptake in jejunum was determined according to the mean standardized uptake value (SUVmean) index. Tissues were also processed in similar time points for histological analysis. RESULTS: The 18F-FDG microPET imaging confirmed the efficacy of telmisartan as a potent attenuating agent for ionizing radiation-induced injury of intestine in mice model. The results were also in line with the histological analysis indicating that pretreatment with telmisartan reduced damage to the villi, crypts, and intestinal mucosa compared with irradiated and non-treated group from day 9 to 30 after irradiation. CONCLUSION: The results revealed that 18F-FDG microPET imaging could be a good candidate to replace time-consuming and invasive biological techniques for screening of radioprotective agents. These findings were also confirmed by histological examinations which indicated that telmisartan can effectively attenuates radiation injury caused by ionizing-irradiation.

Histopathological Evaluation of Protective Effect of Telmisartan against Radiation-Induced Bone Marrow Injury.

Background: Radiation-induced hematopoietic suppression and myelotoxicity can occur due to the nuclear accidents, occupational irradiation and therapeutic interventions. Bone marrow dysfunction has always been one of the most important causes of morbidity and mortality after ionizing irradiation. Objective: This study aims to investigate the protective effect of telmisartan against radiation-induced bone marrow injuries in a Balb/c mouse model. Material and Methods: In this experimental study, male Balb/c mice were divided into four groups as follow: group 1: mice received phosphate buffered saline (PBS) without irradiation, group 2: mice received a solution of telmisartan in PBS without irradiation, group 3: mice received PBS with irradiation, and group 4: mice received a solution of telmisartan in PBS with irradiation. A solution of telmisartan was prepared and administered orally at 12 mg/kg body weight for seven consecutive days prior to whole body exposing to a single sub-lethal dose of 5 Gy X-rays. Protection of bone marrow against radiation induced damage was investigated by Hematoxylin-Eosin (HE) staining assay at 3, 9, 15 and 30 days after irradiation. Results: Histopathological analysis indicated that administration of telmisartan reduced X-radiation-induced damage and improved bone marrow histology. The number of different cell types in bone marrow, including polymorphonuclear /mononuclear cells and megakaryocytes significantly increased in telmisartan treated group compared to the only irradiated group at all-time points. Conclusion: The results of the present study demonstrated an efficient radioprotective effect of telmisartan in mouse bone marrow against sub-lethal X-irradiation.

Leveraging deep neural networks to improve numerical and perceptual image quality in low-dose preclinical PET imaging.

The amount of radiotracer injected into laboratory animals is still the most daunting challenge facing translational PET studies. Since low-dose imaging is characterized by a higher level of noise, the quality of the reconstructed images leaves much to be desired. Being the most ubiquitous techniques in denoising applications, edge-aware denoising filters, and reconstruction-based techniques have drawn significant attention in low-count applications. However, for the last few years, much of the credit has gone to deep-learning (DL) methods, which provide more robust solutions to handle various conditions. Albeit being extensively explored in clinical studies, to the best of our knowledge, there is a lack of studies exploring the feasibility of DL-based image denoising in low-count small animal PET imaging. Therefore, herein, we investigated different DL frameworks to map low-dose small animal PET images to their full-dose equivalent with quality and visual similarity on a par with those of standard acquisition. The performance of the DL model was also compared to other well-established filters, including Gaussian smoothing, nonlocal means, and anisotropic diffusion. Visual inspection and quantitative assessment based on quality metrics proved the superior performance of the DL methods in low-count small animal PET studies, paving the way for a more detailed exploration of DL-assisted algorithms in this domain.

Advances in Preclinical PET Instrumentation.

In the light of ever-increasing demands for PET scanner with better resolvability, higher sensitivity and wide accessibility for noninvasive screening of small structures and physiological processes in laboratory rodents, several dedicated PET scanners were developed and evaluated. Understanding conceptual design constraints pros and cons of different configurations and impact of the major components will be helpful to further establish the crucial role of these miniaturized systems in a broad spectrum of modern research. Hence, a comprehensive review of preclinical PET scanners developed till early 2020 with particular emphasis on innovations in instrumentation and geometrical designs is provided.

NEMA NU-4 2008 performance evaluation of Xtrim-PET: A prototype SiPM-based preclinical scanner.

PURPOSE: Xtrim-PET is a newly designed Silicon Photomultipliers (SiPMs)-based prototype PET scanner dedicated for small laboratory animal imaging. We present the performance evaluation of the Xtrim-PET scanner following NEMA NU-4 2008 standards to help optimizing scanning protocols which can be achieved through standard and reliable system performance characterization. METHODS: The performance assessment was conducted according to the National Electrical Manufacturers Association (NEMA) NU-4 2008 standards in terms of spatial resolution, sensitivity, counting rate performance, scatter fraction and image quality. The in vivo imaging capability of the scanner is also showcased through scanning a normal mouse injected with 18 F-FDG. Furthermore, the performance characteristics of the developed scanner are compared with commercially available systems and current prototypes. RESULTS: The volumetric spatial resolution at 5 mm radial offset from the central axis of the scanner is 6.81 µl, whereas a peak absolute sensitivity of 2.99% was achieved using a 250-650 keV energy window and a 10 ns timing window. The peak noise-equivalent count rate (NECR) using a mouse-like phantom is 113.18 kcps at 0.34 KBq/cc with 12.5% scatter fraction, whereas the NECR peaked at 82.76 kcps for an activity concentration level of 0.048 KBq/cc with a scatter fraction of 25.8% for rat-like phantom. An excellent uniformity (3.8%) was obtained using NEMA image quality phantom. Recovery coefficients of 90%, 86%, 68%, 40% and 12% were calculated for rod diameters of 5, 4, 3, 2 and 1 mm, respectively. Spill-over ratios for air-filled and water-filled chambers were 35% and 25% without applying any correction for attenuation and Compton scattering effects. CONCLUSION: Our findings revealed that beyond compactness, lightweight, easy installation and good energy resolution, the Xtrim-PET prototype presents a reasonable performance making it suitable for preclinical molecular imaging-based research.