Background Optimizing intranasal distribution and retention of nasal sprays is essential in the management of patients with chronic rhinosinusitis (CRS), including those that have had functional endoscopic sinus surgery (FESS). Despite multiple existing distribution studies, there remains a need for a technique that allows regionalization of particle deposition within a patient's unique 3‐dimensional (3D) geometry without exposing the patient to radiation. Methods Seven participants delivered normal saline containing a gadolinium‐based contrast agent (GBCA) by either saline irrigation or nasal sprays on 1 side of the nasal cavity. The saline irrigation group included 2 participants (both healthy) while the nasal spray group included 5 participants (2 healthy, 2 post‐FESS patients, 1 CRS patient without any sinus surgery). The distribution of new signal enhancement was assessed on each participant using magnetic resonance imaging (MRI). Serial scans were performed over an interval of 4 minutes in the nasal spray group to assess changes in intranasal distribution over time. Results Signal enhancement was widespread within the nasal cavities and maxillary sinuses of participants (both healthy) that underwent sinus irrigation. For the nasal spray participants, the hotspots for signal enhancement were similar regardless of disease status or previous history of surgery. These included the internal nasal valve, anterior septum, inferior surface of the inferior turbinate, nasal floor, and nasopharynx. No signal enhancement was detected with nasal sprays in either unoperated or operated paranasal sinuses. Conclusion A technique has been developed using MRI evaluation of radioopaque contrast to characterize the temporospatial distribution of topical drug delivery within the sinonasal cavities.
The study of spontaneous mutations in mice over the last century has been fundamental to our understanding of normal physiology and mechanisms of disease. Here we studied the phenotype and genotype of a novel mouse model we have called the New Zealand Ginger (NZG/Kgm) mouse. NZG/Kgm mice are very large, rapidly growing, ginger-colored mice with pink eyes. Breeding NZG/Kgm mice with CAST/Ei or C57BL/6J mice showed that the ginger coat colour is a recessive trait, while the excessive body weight and large body size exhibit a semidominant pattern of inheritance. Backcrossing F1 (NZG/Kgm × CAST/Ei) to NZG/Kgm mice to produce the N2 generation determined that the NZG/Kgm mouse has two recessive pigmentation variant genes ( oca2 p and tyrp-1 b ) and that the tyrp-1 b gene locus associates with large body size. Three coat colors appeared in the N2 generation; ginger, brown, and dark. Strikingly, N2 male coat colour associated with body weight; the brown-colored mice weighed the most followed by ginger and then dark. The male brown coat-colored offspring reached adult body weights indistinguishable from NZG/Kgm males. The large NZG/Kgm mouse body size is a result of excessive lean body mass since these mice are not obese or diabetic. NZG/Kgm mice exhibit an unusual pattern of fat distribution; compared with other mouse strains they have disproportionately higher amounts of subcutaneous and gonadal fat. These mice are susceptible to high-fat diet-induced obesity but are resistant to high-fat diet-induced diabetes. We propose NZG/Kgm mice as a novel model to delineate gene(s) that regulate 1) growth and metabolism, 2) resistance to Type 2 diabetes, and 3) preferential fat deposition in the subcutaneous and gonadal areas.
Purpose or ObjectiveThe accuracy of radiotherapy dose calculation from cone beam computerised tomography (CBCT) depends on estimation of the electron density accounting for beam hardening, the effects of metal artefacts and inhomogeneous object scatter.However, this is made challenging by the inherent sampling deficit in CBCT and the desire to minimise patient dose.Several studies have considered this problem from the point of view of reconstruction, registration or a combination of the two.Here we present the enhanced electron density and dose planning accuracy made possible by a new direct quantitative reconstruction method called Polyquant. Material and MethodsThe stereotactic end-to-end verification (STEEV) phantom patient, Model 038, was used for this study (CIRS, Norfolk, VA, USA).Using a 1 mm head protocol planning fan beam CT images were acquired on a Philips Brilliance Big Bore CT scanner fitted with a flat couch (Philips, Amsterdam, The Netherlands).Treatment plans were prepared using the Eclipse treatment planning system (Varian Medical Systems, Inc., Palo Alto, CA, USA) for a 200 MU 10x10 cm 2 field delivered at 9 gantry angles and the dose calculated at a predetermined reference point.The STEEV phantom was set up on a Varian Truebeam linear accelerator and CBCT images acquired using the on-board imager with the preset head acquisition protocol.Physical dose measurements were acquired using a Pinpoint ionization chamber (PTW, Freiburg, Germany) inserted into the dosimetry cavity of the STEEV phantom.Using the 'raw' CBCT projections standard Feldkamp, Davis and Kress (FDK) reconstruction was carried out.Quantitative reconstruction was also performed using our new Polyquant method.Dose calculation was carried out on the FDK-CBCT and the Polyquant-CBCT images on Eclipse and compared to the physical measurement. ResultsQuantitative results from the physical measurements on the STEEV phantom compared to the calculated dose by Eclipse using the planning CT, FDK-CBCT and Polyquant-CBCT are shown in Table 1 andFigure 1.Not only is the error reduced from the FDK-CBCT result, but the Polyquant reconstruction significantly outperforms the planning CT accuracy with a 26.5% reduction in error.This may be a surprising result due to the usual superiority of fan-beam CT, from its heavily reduced scatter over CBCT, and the routine use of this modality in practice for planning.We would expect that if we had access to the raw data from the fan-beam CT also, the Polyquant applied to this would likely result in better accuracy still.
Mice with a targeted mutation in the pro-opiomelanocortin (Pomc) gene (Pomctm1/tm1 mice) are unable to synthesize desacetyl-α-MSH and α-MSH and they develop obesity when fed chow diet. In this study, we hypothesized that a chronic high-fat (HF) diet exacerbates Pomctm1/tm1 mouse obesity. Male and female Pomcwt/wt and Pomctm1/tm1 mice were fed low-fat (LF) (10 kcal percent fat) or HF (45 kcal percent fat) diets from weaning for 23 weeks. We show that Pomctm1/tm1 mouse obesity is sexually dimorphic and exacerbated by an HF diet. Male Pomctm1/tm1 mice develop obesity because they are hyperphagic compared with Pomcwt/wt mice when fed an LF or HF diet. Female Pomctm1/tm1 mice develop obesity when feeding on an LF or HF diet because they exhibit signs of reduced energy expenditure (no change in feed efficiency; body weight gained exceeding energy intake) compared with Pomcwt/wt mice. A chronic HF diet exacerbates male Pomctm1/tm1 and Pomcwt/wt mouse obesity, and the increased energy intake fully accounts for increased weight gain. In contrast, female Pomcwt/wt mice are protected from chronic HF diet–induced obesity because they reduce the amount of HF diet eaten, and they appear to increase their energy expenditure (no change in feed efficiency but energy intake exceeding body weight gained). A chronic HF diet exacerbates female Pomctm1/tm1 mouse obesity due to impaired ability to reduce the amount of HF diet eaten and apparent impaired HF diet–induced adaptive thermogenesis. Our data show that desacetyl-α-MSH and α-MSH are required for sexually dimorphic HF diet–induced C57BL/6J obesity. In conclusion, desacetyl-α-MSH and α-MSH play salutary roles in sexually dimorphic melanocortin obesity and sexually dimorphic HF diet–induced C57BL/6J obesity.
Background The societal cost of shoulder disabilities in our aging society keeps rising. Providing biomarkers of early changes in the microstructure of rotator cuff (RC) muscles might improve surgical planning. Elevation angle (E1A) and pennation angle (PA) assessed by ultrasound change with RC tears. Furthermore, ultrasounds lack repeatability. Purpose To propose a repeatable framework to quantify the myocyte angulation in RC muscles. Study Type Prospective. Subjects Six asymptomatic healthy volunteers (1 female aged 30 years; 5 males, mean age 35 years, range 25–49 years), who underwent three repositioned scanning sessions (10 minutes apart) of the right infraspinatus muscle (ISPM) and supraspinatus muscle (SSPM). Field Strength/Sequence 3‐T, T1‐weighted and diffusion tensor imaging (DTI; 12 gradient encoding directions, b ‐values of 500 and 800 s/mm 2 ). Assessment Each voxel was binned in percentage of depth defined by the shortest distance in the antero‐posterior direction (manual delineation), i.e. the radial axis. A second order polynomial fit for PA across the muscle depth was used, while E1A described a sigmoid across depth: . Statistical Tests Repeatability was assessed with the nonparametric Wilcoxon's rank‐sum test for paired comparisons across repeated scans in each volunteer for each anatomical muscle region and across repeated measures of the radial axis. A P ‐value <0.05 was considered statistically significant. Results In the ISPM, E1A was constantly negative, became helicoidal, then mainly positive across the antero‐posterior depth, respective at the caudal, central and cranial regions. In the SSPM, posterior myocytes ran more parallel to the intramuscular tendon (), while anterior myocytes inserted with a pennation angle (). E1A and PA were repeatable in each volunteer (error < 10%). Intra‐repeatability of the radial axis was achieved (error < 5%). Data Conclusion ElA and PA in the proposed framework of the ISPM and SSPM are repeatable with DTI. Variations of myocyte angulation in the ISPM and SSPM can be quantified across volunteers. Evidence Level 2 Technical Efficacy Stage 2
Magnetic resonance imaging (MRI) guided cardiac radioablation (CR) for atrial fibrillation (AF) is a promising treatment concept. However, the visibility of AF CR targets on MRI acquisitions requires further exploration and MRI sequence and parameter optimization has not yet been performed for this application. This pilot study explores the feasibility of MRI-guided tracking of AF CR targets by evaluating AF CR target visualization on human participants using a selection of 3D and 2D MRI sequences.MRI datasets were acquired in healthy and AF participants using a range of MRI sequences and parameters. MRI acquisition categories included 3D free-breathing acquisitions (3Dacq), 2D breath-hold ECG-gated acquisitions (2DECG-gated), stacks of 2D breath-hold ECG-gated acquisitions which were retrospectively interpolated to 3D datasets (3Dinterp), and 2D breath-hold ungated acquisitions (2Dreal-time). The ease of target delineation and the presence of artifacts were qualitatively analyzed. Image quality was quantitatively analyzed using signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and non-uniformity. Confident 3D target delineation was achievable on all 3Dinterp datasets but was not possible on any of the 3Dacq datasets. Fewer artifacts and significantly better SNR, CNR and non-uniformity metrics were observed with 3Dinterp compared to 3Dacq. 2Dreal-time datasets had slightly lower SNR and CNR than 2DECG-gated and 3Dinterp n datasets. AF CR target visualization on MRI was qualitatively and quantitatively evaluated. The study findings indicate that AF CR target visualization is achievable despite the imaging challenges associated with these targets, warranting further investigation into MRI-guided AF CR treatments.
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