Characterizing the Myoarchitecture of the Supraspinatus and Infraspinatus Muscles With MRI Using Diffusion Tensor Imaging.

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/mm2 ). 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: E 1 A sig = E 1 A range × sigmf 1 : 100 % depth , - EA 1 grad   ,   E 1 A asym + E 1 A shift . 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 ( PA ≈ 0 ° ), while anterior myocytes inserted with a pennation angle ( PA ≈ - 20 ° ). 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 shows spinal curvature in Chinook salmon (Oncorhynchus tshawytscha) is associated with chronic inflammation of peri-vertebral soft tissues.

Chinook salmon (Oncorhynchus tshawytscha) farmed in New Zealand are known to develop abnormal spinal curvature late in seawater production. Its cause is presently unknown, but there is evidence to suggest a neuromuscular pathology. Using magnetic resonance imaging (MRI), we evaluated the relationship between soft tissue pathology and spinal curvature in farmed Chinook salmon. Regions of interest (ROIs) presenting as pathologic MRI signal hyper-intensity were identified from scans of 24 harvest-sized individuals: 13 with radiographically-detectable spinal curvature and 11 without. ROIs were excised from individuals using anatomical landmarks as reference points and histologically analysed. Pathologic MRI signal was observed more frequently in individuals with radiographic curvature (92%, n = 12) than those without (18%, n = 2), was localized to the peri-vertebral connective tissues and musculature, and presented as three forms: inflammation, fibrosis, or both. These pathologies are consistent with a chronic inflammatory process, such as that observed during recovery from a soft tissue injury, and suggest spinal curvature in farmed Chinook salmon may be associated with damage to and/or compromised integrity of the peri-vertebral soft tissues. Future research to ascertain the contributing factors is required.

Quinapril treatment curtails decline of global longitudinal strain and mechanical function in hypertensive rats.

BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) has been proposed as an early imaging biomarker of cardiac mechanical dysfunction. OBJECTIVE: To assess the impact of angiotensin-converting enzyme (ACE) inhibitor treatment of hypertensive heart disease on LV GLS and mechanical function. METHODS: The spontaneously hypertensive rat (SHR) model of hypertensive heart disease ( n  = 38) was studied. A subset of SHRs received quinapril (TSHR, n  = 16) from 3 months (mo). Wistar Kyoto rats (WKY, n  = 13) were used as controls. Tagged cardiac MRI was performed using a 4.7 T Varian preclinical scanner. RESULTS: The SHRs had significantly lower LV ejection fraction (EF) than the WKYs at 3 mo (53.0 ±â€Š1.7% vs. 69.6 ±â€Š2.1%, P  < 0.05), 14 mo (57.0 ±â€Š2.5% vs. 74.4 ±â€Š2.9%, P  < 0.05) and 24 mo (50.1 ±â€Š2.4% vs. 67.0 ±â€Š2.0%, P  < 0.01). At 24 mo, ACE inhibitor treatment was associated with significantly greater LV EF in TSHRs compared to untreated SHRs (64.2 ±â€Š3.4% vs. 50.1 ±â€Š2.4%, P  < 0.01). Peak GLS magnitude was significantly lower in SHRs compared with WKYs at 14 months (7.5% ±â€Š0.4% vs. 9.9 ±â€Š0.8%, P  < 0.05). At 24 months, Peak GLS magnitude was significantly lower in SHRs compared with both WKYs (6.5 ±â€Š0.4% vs. 9.7 ±â€Š1.0%, P  < 0.01) and TSHRs (6.5 ±â€Š0.4% vs. 9.6 ±â€Š0.6%, P  < 0.05). CONCLUSIONS: ACE inhibitor treatment curtails the decline in global longitudinal strain in hypertensive rats, with the treatment group exhibiting significantly greater LV EF and GLS magnitude at 24 mo compared with untreated SHRs.

Effect of Gray Value Discretization and Image Filtration on Texture Features of the Pancreas Derived from Magnetic Resonance Imaging at 3T.

Radiomics of pancreas magnetic resonance (MR) images is positioned well to play an important role in the management of diseases characterized by diffuse involvement of the pancreas. The effect of image pre-processing configurations on these images has been sparsely investigated. Fifteen individuals with definite chronic pancreatitis (an exemplar diffuse disease of the pancreas) and 15 healthy individuals were included in this age- and sex-matched case-control study. MR images of the pancreas were acquired using a single 3T scanner. A total of 93 first-order and second-order texture features of the pancreas were compared between the study groups, by subjecting MR images of the pancreas to 7 image pre-processing configurations related to gray level discretization and image filtration. The studied parameters of intensity discretization did not vary in terms of their effect on the number of significant first-order texture features. The number of statistically significant first-order texture features varied after filtering (7 with the use of logarithm filter and 3 with the use of Laplacian of Gaussian filter with 5 mm σ). Intensity discretization generally affected the number of significant second-order texture features more markedly than filtering. The use of fixed bin number of 16 yielded 42 significant second-order texture features, fixed bin number of 128-38 features, fixed bin width of 6-24 features, and fixed bin width of 42-26 features. The specific parameters of filtration and intensity discretization had differing effects on radiomics signature of the pancreas. Relative discretization with fixed bin number of 16 and use of logarithm filter hold promise as pre-processing configurations of choice in future radiomics studies in diffuse diseases of the pancreas.

Atrial fibrillation cardiac radioablation target visibility on magnetic resonance imaging.

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.

Towards developing a robust radiomics signature in diffuse diseases of the pancreas: Accuracy and stability of features derived from T1-weighted magnetic resonance imaging.

BACKGROUND: Radiomics of the pancreas has the potential to personalize the management of patients with diseases that are characterized by diffuse involvement of the pancreas. However, to date, radiomics features that are both clinically useful and reproducible have not been reported. METHODS: Individuals with definite chronic pancreatitis and healthy individuals, matched on sex and age, were prospectively recruited and underwent T1-weighted magnetic resonance imaging of the pancreas at 3T. A total of 107 radiomics features (shape, first-order texture, and second-order texture) were extracted using PyRadiomics and compared between the two groups, taking into account false discovery rate. Stability of significant texture features was investigated by subjecting magnetic resonance images of the pancreas to two core non-overlapping image pre-processing methods - intensity normalization and intensity discretisation. RESULTS: Thirty-one (28.9%) radiomics features were significantly different between the two groups. These included 6 shape features, 6 first-order texture features, and 19 second-order texture features. 'Kurtosis' was significantly different between the two groups after both intensity normalization and intensity discretisation. 'Total energy', 'energy', 'mean', 'root mean squared', '10th percentile', and 'GLCM correlation' were significantly different between the two groups after intensity discretisation. CONCLUSION: The identified radiomics features that are both accurate in characterizing definite diffuse changes in the pancreas morphology and stable irrespective of computational settings (and, therefore, reproducible) are positioned well to form the basis for development of a robust radiomics signature in diffuse diseases of the pancreas.

MRI-guided cardiac-induced target motion tracking for atrial fibrillation cardiac radioablation.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) cardiac radioablation (CR) challenges radiotherapy tracking: multiple small targets close to organs-at-risk undergo rapid differential cardiac contraction and respiratory motion. MR-guidance offers a real-time target tracking solution. This work develops and investigates MRI-guided tracking of AF CR targets with cardiac-induced motion. MATERIALS AND METHODS: A direct tracking method (Trackingdirect) and two indirect tracking methods leveraging population-based surrogacy relationships with the left atria (Trackingindirect_LA) or other target (Trackingindirect_target) were developed. Tracking performance was evaluated using transverse ECG-gated breathhold MRI images from 15 healthy and 10 AF participants. Geometric and volumetric tracking errors were calculated, defined as the difference between the ground-truth and tracked target centroids and volumes respectively. Transverse, breath-hold, noncardiac-gated cine images were acquired at 4 Hz in 5 healthy and 5 AF participants to qualitatively characterize tracking performance on images more comparable to MRILinac acquisitions. RESULTS: The average 3D geometric tracking errors for Trackingdirect, Trackingindirect_LA and Trackingindirect_target respectively were 1.7 ± 1.2 mm, 1.6 ± 1.1 mm and 1.9 ± 1.3 mm in healthy participants and 1.7 ± 1.3 mm, 1.5 ± 1.0 mm and 1.7 ± 1.2 mm in AF participants. For Trackingdirect, 88% of analyzed images had 3D geometric tracking errors <3 mm and the average volume tracking error was 1.7 ± 1.3 cc. For Trackingdirect on non-cardiac-gated cine images, tracked targets overlapped organsat-risk or completely missed the target area on 2.2% and 0.08% of the images respectively. CONCLUSION: The feasibility of non-invasive MRI-guided tracking of cardiac-induced AF CR target motion was demonstrated for the first time, showing potential for improving AF CR treatment efficacy.

Cardiac radioablation for atrial fibrillation: Target motion characterization and treatment delivery considerations.

PURPOSE: The safe delivery of cardiac radioablation (CR) for atrial fibrillation (AF) is challenged by multi-direction target motion, cardiac rate variability, target proximity to critical structures, and the importance of complete target dose coverage for therapeutic benefit. Careful selection of appropriate treatment procedures is therefore essential. This work characterizes AF cardiac radioablation target motion and target proximity to surrounding structures in both healthy and AF participants to guide optimal treatment technique and technology choice. METHODS: Ten healthy participants and five participants with AF underwent MRI acquisition. Multi-slice, cardiac-gated, breath-hold cines were acquired and interpolated to create three-dimensional images for 18-30 cardiac phases. Treatment targets at the left and right pulmonary vein ostia (CTVLeft and CTVRight respectively) and adjacent cardiac structures were contoured and their displacements throughout the cardiac cycle were assessed. Target proximity to surrounding structures were measured. Free-breathing real-time two-dimensional cine images were also acquired at 4 Hz frequency for between 1- and 2-min duration. The motion of easily identifiable points within the target, diaphragm and sternum was measured to assess respiratory motion. RESULTS: Target motion due to cardiac contraction was most prominent in the medial-lateral direction and of 4-5 mm magnitude. CTVRight displacements were smaller in participants with AF than healthy participants in normal sinus rhythm. Nearby cardiac structures often moved with different magnitudes and motion trajectories. CTVLeft and/or CTVRight were in direct contact with the esophagus in 73% of participants. Target motion due to respiration was most prominent in the superior-inferior direction and of 13-14 mm magnitude in both healthy and AF participants. CONCLUSION: AF CR target motion and relative displacement was characterized. The combination of target motion magnitude and relative displacement to critical structures highlights the importance of personalizing motion compensation techniques for effective AF CR treatments.

Pancreas image mining: a systematic review of radiomics.

OBJECTIVES: To systematically review published studies on the use of radiomics of the pancreas. METHODS: The search was conducted in the MEDLINE database. Human studies that investigated the applications of radiomics in diseases of the pancreas were included. The radiomics quality score was calculated for each included study. RESULTS: A total of 72 studies encompassing 8863 participants were included. Of them, 66 investigated focal pancreatic lesions (pancreatic cancer, precancerous lesions, or benign lesions); 4, pancreatitis; and 2, diabetes mellitus. The principal applications of radiomics were differential diagnosis between various types of focal pancreatic lesions (n = 19), classification of pancreatic diseases (n = 23), and prediction of prognosis or treatment response (n = 30). Second-order texture features were most useful for the purpose of differential diagnosis of diseases of the pancreas (with 100% of studies investigating them found a statistically significant feature), whereas filtered image features were most useful for the purpose of classification of diseases of the pancreas and prediction of diseases of the pancreas (with 100% of studies investigating them found a statistically significant feature). The median radiomics quality score of the included studies was 28%, with the interquartile range of 22% to 36%. The radiomics quality score was significantly correlated with the number of extracted radiomics features (r = 0.52, p < 0.001) and the study sample size (r = 0.34, p = 0.003). CONCLUSIONS: Radiomics of the pancreas holds promise as a quantitative imaging biomarker of both focal pancreatic lesions and diffuse changes of the pancreas. The usefulness of radiomics features may vary depending on the purpose of their application. Standardisation of image acquisition protocols and image pre-processing is warranted prior to considering the use of radiomics of the pancreas in routine clinical practice. KEY POINTS: • Methodologically sound studies on radiomics of the pancreas are characterised by a large sample size and a large number of extracted features. • Optimisation of the radiomics pipeline will increase the clinical utility of mineable pancreas imaging data. • Radiomics of the pancreas is a promising personalised medicine tool in diseases of the pancreas.

Ex vivo cardiovascular magnetic resonance diffusion weighted imaging in congenital heart disease, an insight into the microstructures of tetralogy of Fallot, biventricular and univentricular systemic right ventricle.

PURPOSE: Common types of congenital heart disease exhibit a variety of structural and functional variations which may be accompanied by changes in the myocardial microstructure. We aimed to compare myocardial architecture from magnetic resonance diffusion tensor imaging (DTI) in preserved pathology specimens. MATERIALS AND METHODS: Pathology specimens (n = 24) formalin-fixed for 40.8 ± 7.9 years comprised tetralogy of Fallot (TOF, n = 10), dextro-transposition of great arteries (D-TGA, n = 8) five with ventricular septal defect (VSD), systemic right ventricle (n = 4), situs inversus totalis (SIT, n = 1) and levo-TGA (L-TGA, n = 1). Specimens were imaged using a custom spin-echo sequence and segmented automatically according to tissue volume fraction. In each specimen T1, T2, fractional anisotropy, mean diffusivity, helix angle (HA) and sheet angle (E2A) were quantified. Pathologies were compared according to their HA gradient, HA asymmetry and E2A mean value in each myocardial segment (anterior, posterior, septal and lateral walls). RESULTS: TOF and D-TGA with VSD had decreased helix angle gradient by - 0.34°/% and remained symmetric in the septum in comparison to D-TGA without VSD. Helix angle range was decreased by 45°. It was associated with a decreased HA gradient in the right ventricular (RV) wall, i.e. predominant circumferential myocytes. The sheet angle in the septum of TOF was opposing those of the left ventricular (LV) free wall. Univentricular systemic RV had the lowest HA gradient (- 0.43°/%) and the highest HA asymmetry (75%). HA in SIT was linear, asymmetric, and reversed with a sign change at about 70% of the depth at mid-ventricle. In L-TGA with VSD, HA was asymmetric (90%) and its gradients were decreased in the septum, anterior and lateral wall. CONCLUSION: The organization of the myocytes as determined by DTI differs between TOF, D-TGA, L-TGA, systemic RV and SIT specimens. These differences in cardiac structure may further enlighten our understanding of cardiac function in these diverse congenital heart diseases.

Relationship between rheological properties and transverse relaxation time (T2) of artificial and porcine vitreous humour.

Vitreous liquefactive processes play an integral role in ocular health. Knowledge of the degree of liquefaction would allow better monitoring of ocular disease progression and enable more informed therapeutic dosing for an individual patient. Presently this process cannot be monitored in a non-invasive manner. Here, we evaluated whether magnetic resonance imaging (MRI) could predict the viscoelasticity and in turn liquefactive state of artificial and biological vitreous humour. Gels comprising identical concentrations of hyaluronic acid and agar ranging from 0.125 to 2.25 mg/ml of each polymer were prepared and their T2 was measured using a turbo-spin echo sequence via 3T clinical MRI. The gels were subsequently subjected to rheological frequency and flow sweeps and trends between T2 and rheological parameters were assessed. The relationship between T2 and vitreous humour rheology was further assessed using ex vivo porcine eyes. An optimised imaging technique improved homogeneity of obtained artificial vitreous humour T2 maps. Strong correlations were observed between T2 and various rheological parameters of the gels. Translation to porcine vitreous humour demonstrated that the T2 of biological tissue was related to its viscoelastic properties. This study shows that T2 can be correlated with various rheological parameters within gels. Future investigations will assess the translatability of these findings to live models.

Magnetic resonance imaging evaluation of the distribution of spray and irrigation devices within the sinonasal cavities.

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.

Chronic High-Fat Diet Exacerbates Sexually Dimorphic Pomctm1/tm1 Mouse Obesity.

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.

Towards validating stent induced micro flow patterns in left main coronary artery bifurcations.

We investigated if blood flow changes induced through the presence of a stent could be detected using in vitro dynamically scaled 4D Phase-Contrast Magnetic Resonance Imaging (PC-MRI). Using idealized and patient-specific left main coronary artery bifurcations, we 3D-printed the dynamically large scaled geometries and incorporated them into a flow circuit for non-invasive acquisition with a higher effective spatial resolution. We tested the effects of using non-Newtonian and Newtonian fluids for the experiment. We also numerically simulated the same geometries in true scale for comparison using computational fluid dynamics (CFD). We found that the experimental setup increased the effective spatial resolution enough to reveal stent induced blood flow changes close to the vessel wall. Non-Newtonian fluid replicated all of the flow field well with a strong agreement with the computed flow field (R2 > 0.9). Fine flow structures were not as prominent for the Newtonian compared to non-Newtonian fluid consideration. In the patient-specific geometry, arterial non-planarity increased the difficulty to capture the near wall slow velocity changes. Findings demonstrate the potential to dynamically scale in vitro 4D MRI flow acquisition for micro blood flow considerations.

In vitro and ex vivo characterisation of an in situ gelling formulation for sustained lidocaine release with potential use following knee arthroplasty.

Sustained lidocaine release via a thermoresponsive poloxamer-based in situ gelling system has the potential to alleviate pain following knee arthroplasty. A previously developed formulation showed a promising drug release profile in synthetic phosphate-buffered saline (PBS). To support the translation of this formulation, ex vivo characterisation was warranted. This study therefore aimed (1) to modify the previously developed formulation to reduce the burst release, (2) to compare the release behaviour into ex vivo human intra-articular fluid (IAF) and PBS and (3) to determine the formulation spread in an ex vivo human knee using magnetic resonance imaging (MRI). All formulations provided sustained release out to 72 h; polyvinyl pyrrolidone was the most effective additive yielding a small yet significant decrease (p < 0.05) in the burst release. Release of lidocaine from the formulation occurred significantly faster into IAF compared to PBS (1.4 times greater release in the first 24 h), correlating with faster rates of gel erosion in IAF. Injection was easily achieved through a 21-gauge (G) needle into the synovial space of a human cadaveric knee, and MRI scans revealed effective spreading of the formulation throughout the joint cavity. The pattern of spread is promising for the drug to reach the widespread nerve endings in the joint capsule; the effect of this spread on release in an in vivo setting will be the subject of future studies. The demonstrated properties indicate that the in situ gelling formulation has the potential to be used clinically to treat post-operative pain following knee arthroplasty.

Atlas-Based Computational Analysis of Heart Shape and Function in Congenital Heart Disease.

Approximately 1% of all babies are born with some form of congenital heart defect. Many serious forms of CHD can now be surgically corrected after birth, which has led to improved survival into adulthood. However, many patients require serial monitoring to evaluate progression of heart failure and determine timing of interventions. Accurate multidimensional quantification of regional heart shape and function is required for characterizing these patients. A computational atlas of single ventricle and biventricular heart shape and function enables quantification of remodeling in terms of z scores in relation to specific reference populations. Progression of disease can then be monitored effectively by longitudinal evaluation of z scores. A biomechanical analysis of cardiac function in relation to population variation enables investigation of the underlying mechanisms for developing pathology. Here, we summarize recent progress in this field, with examples in single ventricle and biventricular congenital pathologies.

Desacetyl-α-melanocyte stimulating hormone and α-melanocyte stimulating hormone are required to regulate energy balance.

OBJECTIVE: Regulation of energy balance depends on pro-opiomelanocortin (POMC)-derived peptides and melanocortin-4 receptor (MC4R). Alpha-melanocyte stimulating hormone (α-MSH) is the predicted natural POMC-derived peptide that regulates energy balance. Desacetyl-α-MSH, the precursor for α-MSH, is present in brain and blood. Desacetyl-α-MSH is considered to be unimportant for regulating energy balance despite being more potent (compared with α-MSH) at activating the appetite-regulating MC4R in vitro. Thus, the physiological role for desacetyl-α-MSH is still unclear. METHODS: We created a novel mouse model to determine whether desacetyl-α-MSH plays a role in regulating energy balance. We engineered a knock in targeted QKQR mutation in the POMC protein cleavage site that blocks the production of both desacetyl-α-MSH and α-MSH from adrenocorticotropin (ACTH1-39). RESULTS: The mutant ACTH1-39 (ACTHQKQR) functions similar to native ACTH1-39 (ACTHKKRR) at the melanocortin 2 receptor (MC2R) in vivo and MC4R in vitro. Male and female homozygous mutant ACTH1-39 (Pomctm1/tm1) mice develop the characteristic melanocortin obesity phenotype. Replacement of either desacetyl-α-MSH or α-MSH over 14 days into Pomctm1/tm1 mouse brain significantly reverses excess body weight and fat mass gained compared to wild type (WT) (Pomcwt/wt) mice. Here, we identify both desacetyl-α-MSH and α-MSH peptides as regulators of energy balance and highlight a previously unappreciated physiological role for desacetyl-α-MSH. CONCLUSIONS: Based on these data we propose that there is potential to exploit the naturally occurring POMC-derived peptides to treat obesity but this relies on first understanding the specific function(s) for desacetyl-α-MSH and α-MSH.

An Open Benchmark Challenge for Motion Correction of Myocardial Perfusion MRI.

Cardiac magnetic resonance perfusion examinations enable noninvasive quantification of myocardial blood flow. However, motion between frames due to breathing must be corrected for quantitative analysis. Although several methods have been proposed, there is a lack of widely available benchmarks to compare different algorithms. We sought to compare many algorithms from several groups in an open benchmark challenge. Nine clinical studies from two different centers comprising normal and diseased myocardium at both rest and stress were made available for this study. The primary validation measure was regional myocardial blood flow based on the transfer coefficient (Ktrans), which was computed using a compartment model and the myocardial perfusion reserve (MPR) index. The ground truth was calculated using contours drawn manually on all frames by a single observer, and visually inspected by a second observer. Six groups participated and 19 different motion correction algorithms were compared. Each method used one of three different motion models: rigid, global affine, or local deformation. The similarity metric also varied with methods employing either sum-of-squared differences, mutual information, or cross correlation. There were no significant differences in Ktrans or MPR compared across different motion models or similarity metrics. Compared with the ground truth, only Ktrans for the sum-of-squared differences metric, and for local deformation motion models, had significant bias. In conclusion, the open benchmark enabled evaluation of clinical perfusion indices over a wide range of methods. In particular, there was no benefit of nonrigid registration techniques over the other methods evaluated in this study. The benchmark data and results are available from the Cardiac Atlas Project ( www.cardiacatlas.org).

Cardiac image modelling: Breadth and depth in heart disease.

With the advent of large-scale imaging studies and big health data, and the corresponding growth in analytics, machine learning and computational image analysis methods, there are now exciting opportunities for deepening our understanding of the mechanisms and characteristics of heart disease. Two emerging fields are computational analysis of cardiac remodelling (shape and motion changes due to disease) and computational analysis of physiology and mechanics to estimate biophysical properties from non-invasive imaging. Many large cohort studies now underway around the world have been specifically designed based on non-invasive imaging technologies in order to gain new information about the development of heart disease from asymptomatic to clinical manifestations. These give an unprecedented breadth to the quantification of population variation and disease development. Also, for the individual patient, it is now possible to determine biophysical properties of myocardial tissue in health and disease by interpreting detailed imaging data using computational modelling. For these population and patient-specific computational modelling methods to develop further, we need open benchmarks for algorithm comparison and validation, open sharing of data and algorithms, and demonstration of clinical efficacy in patient management and care. The combination of population and patient-specific modelling will give new insights into the mechanisms of cardiac disease, in particular the development of heart failure, congenital heart disease, myocardial infarction, contractile dysfunction and diastolic dysfunction.

Improving assessment of congenital heart disease through rapid patient specific modeling.

Congenital heart disease is the most common birth defect, with an incidence of 75 in every 1000 births. As a result of improved interventions, 90% of people with congenital heart disease now survive to adulthood. They must undergo regular imaging to assess their biventricular (left and right ventricular) function. Analysis of the images is problematic due to the large variety of shapes and complex geometry. In this paper we extend a biventricular modeling method to improve the analysis of MR images from congenital heart disease patients. We used a subdivision surface method to create three customizable exemplars, representing common manifestations of anatomy, and incorporated these as priors into an interactive biventricular customization procedure. The CHD-specific priors were tested on 60 cases representing a variety of congenital heart diseases for which the gold standard manual contours were available. The introduction of multiple priors showed a significant decrease in analysis time while maintaining good correlation between the two methods (R2 >.82).