Preliminary study of proton magnetic resonance spectroscopy to assess bone marrow adiposity in the third metacarpus or metatarsus in Thoroughbred racehorses.

BACKGROUND: Magnetic resonance spectroscopy (MRS) has been used to investigate metabolic changes within human bone. It may be possible to use MRS to investigate bone metabolism and fracture risk in the distal third metacarpal/tarsal bone (MC/MTIII) in racehorses. OBJECTIVES: To determine the feasibility of using MRS as a quantitative imaging technique in equine bone by using the 1H spectra for the MC/MTIII to calculate fat content (FC). STUDY DESIGN: Observational cross-sectional study. METHODS: Limbs from Thoroughbred racehorses were collected from horses that died or were subjected to euthanasia on racecourses. Each limb underwent magnetic resonance imaging (MRI) at 3 T followed by single-voxel MRS at three regions of interest (ROI) within MC/MTIII (lateral condyle, medial condyle, proximal bone marrow [PBM]). Percentage FC was calculated at each ROI. Each limb underwent computed tomography (CT) and bone mineral density (BMD) was calculated for the same ROIs. All MR and CT images were graded for sclerosis. Histology slides were graded for sclerosis and proximal marrow space was calculated. Pearson or Spearman correlations were used to assess the relationship between BMD, FC and marrow space. Kruskal-Wallis tests were used to check for differences between sclerosis groups for BMD or FC. RESULTS: Eighteen limbs from 10 horses were included. A negative correlation was identified for mean BMD and FC for the lateral condyle (correlation coefficient = -0.60, p = 0.01) and PBM (correlation coefficient = -0.5, p = 0.04). There was a significant difference between median BMD for different sclerosis grades in the condyles on both MRI and CT. A significant difference in FC was identified between sclerosis groups in the lateral condyle on MRI and CT. MAIN LIMITATIONS: Small sample size. CONCLUSIONS: 1H Proton MRS is feasible in the equine MC/MTIII. Further work is required to evaluate the use of this technique to predict fracture risk in racehorses.

TIST-Net: style transfer in dynamic contrast enhanced MRI using spatial and temporal information.

Objective.Training deep learning models for image registration or segmentation of dynamic contrast enhanced (DCE) MRI data is challenging. This is mainly due to the wide variations in contrast enhancement within and between patients. To train a model effectively, a large dataset is needed, but acquiring it is expensive and time consuming. Instead, style transfer can be used to generate new images from existing images. In this study, our objective is to develop a style transfer method that incorporates spatio-temporal information to either add or remove contrast enhancement from an existing image.Approach.We propose a temporal image-to-image style transfer network (TIST-Net), consisting of an auto-encoder combined with convolutional long short-term memory networks. This enables disentanglement of the content and style latent spaces of the time series data, using spatio-temporal information to learn and predict key structures. To generate new images, we use deformable and adaptive convolutions which allow fine grained control over the combination of the content and style latent spaces. We evaluate our method, using popular metrics and a previously proposed contrast weighted structural similarity index measure. We also perform a clinical evaluation, where experts are asked to rank images generated by multiple methods.Main Results.Our model achieves state-of-the-art performance on three datasets (kidney, prostate and uterus) achieving an SSIM of 0.91 ± 0.03, 0.73 ± 0.04, 0.88 ± 0.04 respectively when performing style transfer between a non-enhanced image and a contrast-enhanced image. Similarly, SSIM results for style transfer from a contrast-enhanced image to a non-enhanced image were 0.89 ± 0.03, 0.82 ± 0.03, 0.87 ± 0.03. In the clinical evaluation, our method was ranked consistently higher than other approaches.Significance.TIST-Net can be used to generate new DCE-MRI data from existing images. In future, this may improve models for tasks such as image registration or segmentation by allowing small training datasets to be expanded.

Contrast-agent-based perfusion MRI code repository and testing framework: ISMRM Open Science Initiative for Perfusion Imaging (OSIPI).

PURPOSE: Software has a substantial impact on quantitative perfusion MRI values. The lack of generally accepted implementations, code sharing and transparent testing reduces reproducibility, hindering the use of perfusion MRI in clinical trials. To address these issues, the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI) aimed to establish a community-led, centralized repository for sharing open-source code for processing contrast-based perfusion imaging, incorporating an open-source testing framework. METHODS: A repository was established on the OSIPI GitHub website. Python was chosen as the target software language. Calls for code contributions were made to OSIPI members, the ISMRM Perfusion Study Group, and publicly via OSIPI websites. An automated unit-testing framework was implemented to evaluate the output of code contributions, including visual representation of the results. RESULTS: The repository hosts 86 implementations of perfusion processing steps contributed by 12 individuals or teams. These cover all core aspects of DCE- and DSC-MRI processing, including multiple implementations of the same functionality. Tests were developed for 52 implementations, covering five analysis steps. For T1 mapping, signal-to-concentration conversion and population AIF functions, different implementations resulted in near-identical output values. For the five pharmacokinetic models tested (Tofts, extended Tofts-Kety, Patlak, two-compartment exchange, and two-compartment uptake), differences in output parameters were observed between contributions. CONCLUSIONS: The OSIPI DCE-DSC code repository represents a novel community-led model for code sharing and testing. The repository facilitates the re-use of existing code and the benchmarking of new code, promoting enhanced reproducibility in quantitative perfusion imaging.

Relationship between CT-Derived Bone Mineral Density and UTE-MR-Derived Porosity Index in Equine Third Metacarpal and Metatarsal Bones.

Fatigue-related subchondral bone injuries of the third metacarpal/metatarsal (McIII/MtIII) bones are common causes of wastage, and they are welfare concerns in racehorses. A better understanding of bone health and strength would improve animal welfare and be of benefit for the racing industry. The porosity index (PI) is an indirect measure of osseous pore size and number in bones, and it is therefore an interesting indicator of bone strength. MRI of compact bone using traditional methods, even with short echo times, fail to generate enough signal to assess bone architecture as water protons are tightly bound. Ultra-short echo time (UTE) sequences aim to increase the amount of signal detected in equine McIII/MtIII condyles. Cadaver specimens were imaged using a novel dual-echo UTE MRI technique, and PI was calculated and validated against quantitative CT-derived bone mineral density (BMD) measures. BMD and PI are inversely correlated in equine distal Mc/MtIII bone, with a weak mean r value of -0.29. There is a statistically significant difference in r values between the forelimbs and hindlimbs. Further work is needed to assess how correlation patterns behave in different areas of bone and to evaluate PI in horses with and without clinically relevant stress injuries.

QCT-based computational bone strength assessment updated with MRI-derived 'hidden' microporosity.

Microdamage accumulated through sustained periods of cyclic loading or single overloading events contributes to bone fragility through a reduction in stiffness and strength. Monitoring microdamage in vivo remains unattainable by clinical imaging modalities. As such, there are no established computational methods for clinical fracture risk assessment that account for microdamage that exists in vivo at any specific timepoint. We propose a method that combines multiple clinical imaging modalities to identify an indicative surrogate, which we term 'hidden porosity', that incorporates pre-existing bone microdamage in vivo. To do so, we use the third metacarpal bone of the equine athlete as an exemplary model for fatigue induced microdamage, which coalesces in the subchondral bone. N = 10 metacarpals were scanned by clinical quantitative computed tomography (QCT) and magnetic resonance imaging (MRI). We used a patch-based similarity method to quantify the signal intensity of a fluid sensitive MRI sequence in bone regions where microdamage coalesces. The method generated MRI-derived pseudoCT images which were then used to determine a pre-existing damage (Dpex) variable to quantify the proposed surrogate and which we incorporate into a nonlinear constitutive model for bone tissue. The minimum, median, and maximum detected Dpex of 0.059, 0.209, and 0.353 reduced material stiffness by 5.9%, 20.9%, and 35.3% as well as yield stress by 5.9%, 20.3%, and 35.3%. Limb-specific voxel-based finite element meshes were equipped with the updated material model. Lateral and medial condyles of each metacarpal were loaded to simulate physiological joint loading during gallop. The degree of detected Dpex correlated with a relative reduction in both condylar stiffness (p = 0.001, R2 > 0.74) and strength (p < 0.001, R2 > 0.80). Our results illustrate the complementary value of looking beyond clinical CT, which neglects the inclusion of microdamage due to partial volume effects. As we use clinically available imaging techniques, our results may aid research beyond the equine model on fracture risk assessment in human diseases such as osteoarthritis, bone cancer, or osteoporosis.

Non-invasive imaging of functional pancreatic islet beta-cell mass in people with type 1 diabetes mellitus.

AIMS: To investigate whether manganese-enhanced magnetic resonance imaging can assess functional pancreatic beta-cell mass in people with type 1 diabetes mellitus. METHODS: In a prospective case-control study, 20 people with type 1 diabetes mellitus (10 with low (≥50 pmol/L) and 10 with very low (<50 pmol/L) C-peptide concentrations) and 15 healthy volunteers underwent manganese-enhanced magnetic resonance imaging of the pancreas following an oral glucose load. Scan-rescan reproducibility was performed in 10 participants. RESULTS: Mean pancreatic manganese uptake was 31 ± 6 mL/100 g of tissue/min in healthy volunteers (median 32 [interquartile range 23-36] years, 6 women), falling to 23 ± 4 and 13 ± 5 mL/100 g of tissue/min (p ≤ 0.002 for both) in people with type1 diabetes mellitus (52 [44-61] years, 6 women) and low or very low plasma C-peptide concentrations respectively. Pancreatic manganese uptake correlated strongly with plasma C-peptide concentrations in people with type1 diabetes mellitus (r = 0.73, p < 0.001) but not in healthy volunteers (r = -0.054, p = 0.880). There were no statistically significant correlations between manganese uptake and age, body-mass index, or glycated haemoglobin. There was strong intra-observer (mean difference: 0.31 (limits of agreement -1.42 to 2.05) mL/100 g of tissue/min; intra-class correlation, ICC = 0.99), inter-observer (-1.23 (-5.74 to 3.27) mL/100 g of tissue/min; ICC = 0.85) and scan-rescan (-0.72 (-2.9 to 1.6) mL/100 g of tissue/min; ICC = 0.96) agreement for pancreatic manganese uptake. CONCLUSIONS: Manganese-enhanced magnetic resonance imaging provides a potential reproducible non-invasive measure of functional beta-cell mass in people with type 1 diabetes mellitus. This holds major promise for investigating type 1 diabetes, monitoring disease progression and assessing novel immunomodulatory interventions.

Manganese-Enhanced Magnetic Resonance Imaging of the Heart.

Manganese-based contrast media were the first in vivo paramagnetic agents to be used in magnetic resonance imaging (MRI). The uniqueness of manganese lies in its biological function as a calcium channel analog, thus behaving as an intracellular contrast agent. Manganese ions are taken up by voltage-gated calcium channels in viable tissues, such as the liver, pancreas, kidneys, and heart, in response to active calcium-dependent cellular processes. Manganese-enhanced magnetic resonance imaging (MEMRI) has therefore been used as a surrogate marker for cellular calcium handling and interest in its potential clinical applications has recently re-emerged, especially in relation to assessing cellular viability and myocardial function. Calcium homeostasis is central to myocardial contraction and dysfunction of myocardial calcium handling is present in various cardiac pathologies. Recent studies have demonstrated that MEMRI can detect the presence of abnormal myocardial calcium handling in patients with myocardial infarction, providing clear demarcation between the infarcted and viable myocardium. Furthermore, it can provide more subtle assessments of abnormal myocardial calcium handling in patients with cardiomyopathies and being excluded from areas of nonviable cardiomyocytes and severe fibrosis. As such, MEMRI offers exciting potential to improve cardiac diagnoses and provide a noninvasive measure of myocardial function and contractility. This could be an invaluable tool for the assessment of both ischemic and nonischemic cardiomyopathies as well as providing a measure of functional myocardial recovery, an accurate prediction of disease progression and a method of monitoring treatment response. EVIDENCE LEVEL: 5: TECHNICAL EFFICACY: STAGE 5.

T2 mapping of cartilage in the equine distal interphalangeal joint with corresponding histology using 0.27 T and 3.0 T magnetic resonance imaging.

BACKGROUND: Low-field magnetic resonance imaging (MRI) is widely available to equine veterinarians yet is insensitive at detecting cartilage damage in the distal interphalangeal joint (DIPJ). T2 mapping is a quantitative imaging technique that can detect cartilage damage before morphological change is apparent. OBJECTIVES: Validation of a T2 mapping sequence on a low-field MR system. Correlation of the mean T2 relaxation time in sections of cartilage with varying levels of pathology using low- and high-field MRI. STUDY DESIGN: Cross-sectional study. METHODS: Eight phantoms with known (nominal) T2 values underwent low-field (0.27 T) MRI and 38 ex vivo DIPJs were imaged. A further 9 ex vivo DIPJs were imaged on both the low- and high-field MR systems. Immediately after imaging, the DIPJs were disarticulated and samples collected for histology. Histological sections were graded using the Osteoarthritis Research Society International (OARSI) scoring system. Fiji ImageJ software with the MRIAnalysisPak plugin was used to calculate T2 maps and draw the regions of interest (ROIs). RESULTS: There was close agreement between the nominal and the measured T2 values in the phantom study. Spearman's rank correlation demonstrated significant positive correlation between low- and high-field T2 measurements, rho 0.644 (p < 0.001). The intrarater agreement for T2 measurements was excellent, intraclass correlation coefficient (ICC) = 0.99 (95% confidence interval [CI] = 0.99-1.00), the inter-rater agreement was excellent, ICC = 0.88 (95% CI = 0.82-0.92) and there was good intrarater agreement for OARSI scores (к = 0.76). MAIN LIMITATIONS: Only a small number of histological samples were analysed. Both articular cartilage surfaces were measured within the ROI. There were no OARSI grade 0 control samples. CONCLUSIONS: A T2 mapping sequence on a low-field 0.27 T MR system was validated. There was a positive correlation between low- and high-field T2 measurements. The findings suggest a higher mean T2 relaxation time in pathological cartilage tissue examined in this study compared to normal equine cartilage tissue.

Manganese-Enhanced Magnetic Resonance Imaging in Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome is an acute cardiac emergency characterized by transient left ventricular systolic dysfunction typically following a stressful event. Despite its rapidly rising incidence, its pathophysiology remains poorly understood. Takotsubo syndrome may pass unrecognized, especially if timely diagnostic imaging is not performed. Defective myocardial calcium homeostasis is a central cause of contractile dysfunction and has not been explored in takotsubo syndrome. We aimed to investigate myocardial calcium handling using manganese-enhanced magnetic resonance imaging during the acute and recovery phases of takotsubo syndrome. METHODS: Twenty patients with takotsubo syndrome (63±12 years of age; 90% female) and 20 volunteers matched on age, sex, and cardiovascular risk factors (59±11 years of age; 70% female) were recruited from the Edinburgh Heart Centre between March 2020 and October 2021. Patients underwent gadolinium and manganese-enhanced magnetic resonance imaging during index hospitalization with repeat manganese-enhanced magnetic resonance imaging performed after at least 3 months. RESULTS: Compared with matched control volunteers, patients had a reduced left ventricular ejection fraction (51±11 versus 67±8%; P<0.001), increased left ventricular mass (86±11 versus 57±14 g/m2; P<0.001), and, in affected myocardial segments, elevated native T1 (1358±49 versus 1211±28 ms; P<0.001) and T2 (60±7 versus 38±3 ms; P<0.0001) values at their index presentation. During manganese-enhanced imaging, kinetic modeling demonstrated a substantial reduction in myocardial manganese uptake (5.1±0.5 versus 8.2±1.1 mL/[100 g of tissue ·min], respectively; P<0.0001), consistent with markedly abnormal myocardial calcium handling. After recovery, left ejection fraction, left ventricular mass, and T2 values were comparable with those of matched control volunteers. Despite this, native and postmanganese T1 and myocardial manganese uptake remained abnormal compared with matched control volunteers (6.6±0.5 versus 8.2±1.1 mL/[100 g of tissue ·min]; P<0.0001). CONCLUSIONS: In patients with takotsubo syndrome, there is a profound perturbation of myocardial manganese uptake, which is most marked in the acute phase but persists for at least 3 months despite apparent restoration of normal left ventricular ejection fraction and resolution of myocardial edema, suggesting abnormal myocardial calcium handling may be implicated in the pathophysiology of takotsubo syndrome. Manganese-enhanced magnetic resonance imaging has major potential to assist in the diagnosis, characterization, and risk stratification of patients with takotsubo syndrome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04623788.

MRI and CT coronary angiography in survivors of COVID-19.

OBJECTIVES: To determine the contribution of comorbidities on the reported widespread myocardial abnormalities in patients with recent COVID-19. METHODS: In a prospective two-centre observational study, patients hospitalised with confirmed COVID-19 underwent gadolinium and manganese-enhanced MRI and CT coronary angiography (CTCA). They were compared with healthy and comorbidity-matched volunteers after blinded analysis. RESULTS: In 52 patients (median age: 54 (IQR 51-57) years, 39 males) who recovered from COVID-19, one-third (n=15, 29%) were admitted to intensive care and a fifth (n=11, 21%) were ventilated. Twenty-three patients underwent CTCA, with one-third having underlying coronary artery disease (n=8, 35%). Compared with younger healthy volunteers (n=10), patients demonstrated reduced left (ejection fraction (EF): 57.4±11.1 (95% CI 54.0 to 60.1) versus 66.3±5 (95 CI 62.4 to 69.8)%; p=0.02) and right (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 60.5±4.9 (95% CI 57.1 to 63.2)%; p≤0.0001) ventricular systolic function with elevated native T1 values (1225±46 (95% CI 1205 to 1240) vs 1197±30 (95% CI 1178 to 1216) ms;p=0.04) and extracellular volume fraction (ECV) (31±4 (95% CI 29.6 to 32.1) vs 24±3 (95% CI 22.4 to 26.4)%; p<0.0003) but reduced myocardial manganese uptake (6.9±0.9 (95% CI 6.5 to 7.3) vs 7.9±1.2 (95% CI 7.4 to 8.5) mL/100 g/min; p=0.01). Compared with comorbidity-matched volunteers (n=26), patients had preserved left ventricular function but reduced right ventricular systolic function (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 59.3±4.9 (95% CI 51.0 to 66.5)%; p=0.0005) with comparable native T1 values (1225±46 (95% CI 1205 to 1240) vs 1227±51 (95% CI 1208 to 1246) ms; p=0.99), ECV (31±4 (95% CI 29.6 to 32.1) vs 29±5 (95% CI 27.0 to 31.2)%; p=0.35), presence of late gadolinium enhancement and manganese uptake. These findings remained irrespective of COVID-19 disease severity, presence of myocardial injury or ongoing symptoms. CONCLUSIONS: Patients demonstrate right but not left ventricular dysfunction. Previous reports of left ventricular myocardial abnormalities following COVID-19 may reflect pre-existing comorbidities. TRIAL REGISTRATION NUMBER: NCT04625075.

Assessment of stunned and viable myocardium using manganese-enhanced MRI.

OBJECTIVE: In a proof-of-concept study, to quantify myocardial viability in patients with acute myocardial infarction using manganese-enhanced MRI (MEMRI), a measure of intracellular calcium handling. METHODS: Healthy volunteers (n=20) and patients with ST-elevation myocardial infarction (n=20) underwent late gadolinium enhancement (LGE) using gadobutrol and MEMRI using manganese dipyridoxyl diphosphate. Patients were scanned ≤7 days after reperfusion and rescanned after 3 months. Differential manganese uptake was described using a two-compartment model. RESULTS: After manganese administration, healthy control and remote non-infarcted myocardium showed a sustained 25% reduction in T1 values (mean reductions, 288±34 and 281±12 ms). Infarcted myocardium demonstrated less T1 shortening than healthy control or remote myocardium (1157±74 vs 859±36 and 835±28 ms; both p<0.0001) with intermediate T1 values (1007±31 ms) in peri-infarct regions. Compared with LGE, MEMRI was more sensitive in detecting dysfunctional myocardium (dysfunctional fraction 40.5±11.9 vs 34.9%±13.9%; p=0.02) and tracked more closely with abnormal wall motion (r2=0.72 vs 0.55; p<0.0001). Kinetic modelling showed reduced myocardial manganese influx between remote, peri-infarct and infarct regions, enabling absolute discrimination of infarcted myocardium. After 3 months, manganese uptake increased in peri-infarct regions (16.5±3.5 vs 22.8±3.5 mL/100 g/min, p<0.0001), but not the remote (23.3±2.8 vs 23.0±3.2 mL/100 g/min, p=0.8) or infarcted (11.5±3.7 vs 14.0±1.2 mL/100 g/min, p>0.1) myocardium. CONCLUSIONS: Through visualisation of intracellular calcium handling, MEMRI accurately differentiates infarcted, stunned and viable myocardium, and correlates with myocardial dysfunction better than LGE. MEMRI holds major promise in directly assessing myocardial viability, function and calcium handling across a range of cardiac diseases. TRIAL REGISTRATION NUMBERS: NCT03607669; EudraCT number 2016-003782-25.

Feasibility of a multiparametric MRI protocol for imaging biomarkers associated with neoadjuvant radiotherapy for soft tissue sarcoma.

Objective: Soft tissue sarcoma (STS) is a rare malignancy with a 5 year overall survival rate of 55%. Neoadjuvant radiotherapy is commonly used in preparation for surgery, but methods to assess early response are lacking despite pathological response at surgery being predictive of overall survival, local recurrence and distant metastasis. Multiparametric MR imaging (mpMRI) is used to assess response in a variety of tumours but lacks a robust, standardised method. The overall aim of this study was to develop a feasible imaging protocol to identify imaging biomarkers for further investigation. Methods: 15 patients with biopsy-confirmed STS suitable for pre-operative radiotherapy and radical surgery were imaged throughout treatment. The mpMRI protocol included anatomical, diffusion-weighted and dynamic contrast-enhanced imaging, giving estimates of apparent diffusion coefficient (ADC) and the area under the enhancement curve at 60 s (iAUC60). Histological analysis of resected tumours included detection of CD31, Ki67, hypoxia inducible factor and calculation of a hypoxia score. Results: There was a significant reduction in T1 at visit 2 and in ADC at visit 3. Significant associations were found between hypoxia and pre-treatment iAUC60, pre-treatment ADC and mid-treatment iAUC60. There was also statistically significant association between mid-treatment ADC and Ki67. Conclusion: This work showed that mpMRI throughout treatment is feasible in patients with STS having neoadjuvant radiotherapy. The relationships between imaging parameters, tissue biomarkers and clinical outcomes warrant further investigation. Advances in knowledge: mpMRI-based biomarkers have good correlation with STS tumour biology and are potentially of use for evaluation of radiotherapy response.

HYPOXIA AND REPRODUCTIVE HEALTH: The presence and role of hypoxia in the endometrium.

The endometrium is a multicellular tissue that is exquisitely responsive to the ovarian hormones. The local mechanisms of endometrial regulation to ensure optimal function are less well characterised. Transient physiological hypoxia has been proposed as a critical regulator of endometrial function. Herein, we review the literature on hypoxia in the non-pregnant endometrium. We discuss the pros and cons of animal models, human laboratory studies and novel in vivo imaging for the study of endometrial hypoxia. These research tools provide mounting evidence of a transient hypoxic episode in the menstrual endometrium and suggest that endometrial hypoxia may be present at the time of implantation. This local hypoxia may modify the inflammatory environment, influence vascular remodelling and modulate endometrial proliferation to optimise endometrial function. Finally, we review current knowledge of the impact of this hypoxia on endometrial pathologies, with a focus on abnormal uterine bleeding. Throughout the manuscript areas for future research are highlighted with the aim of concentrating research efforts to maximise future benefits for women and society.

Advanced imaging for quantification of abnormalities in the salivary glands of patients with primary Sjögren's syndrome.

OBJECTIVES: To assess non-invasive imaging for detection and quantification of gland structure, inflammation and function in patients with primary Sjogren's syndrome (pSS) using PET-CT with 11C-Methionine (11C-MET; radiolabelled amino acid), and 18F-fluorodeoxyglucose (18F-FDG; glucose uptake marker), to assess protein synthesis and inflammation, respectively; multiparametric MRI evaluated salivary gland structural and physiological changes. METHODS: In this imaging/clinical/histology comparative study (GSK study 203818; NCT02899377) patients with pSS and age- and sex-matched healthy volunteers underwent MRI of the salivary glands and 11C-MET PET-CT. Patients also underwent 18F-FDG PET-CT and labial salivary gland biopsies. Clinical and biomarker assessments were performed. Primary endpoints were semi-quantitative parameters of 11C-MET and 18F-FDG uptake in submandibular and parotid salivary glands and quantitative MRI measures of structure and inflammation. Clinical and minor salivary gland histological parameter correlations were explored. RESULTS: Twelve patients with pSS and 13 healthy volunteers were included. Lower 11C-MET uptake in parotid, submandibular and lacrimal glands, lower submandibular gland volume, higher MRI fat fraction, and lower pure diffusion in parotid and submandibular glands were observed in patients vs healthy volunteer, consistent with reduced synthetic function. Disease duration correlated positively with fat fraction and negatively with 11C-MET and 18F-FDG uptake, consistent with impaired function, inflammation and fatty replacement over time. Lacrimal gland 11C-MET uptake positively correlated with tear flow in patients, and parotid gland 18F-FDG uptake positively correlated with salivary gland CD20+ B-cell infiltration. CONCLUSION: Molecular imaging and MRI may be useful tools to non-invasively assess loss of glandular function, increased glandular inflammation and fat accumulation in pSS.

Does magnetic resonance imaging improve soft tissue sarcoma contouring for radiotherapy?

OBJECTIVE: Soft tissue sarcomas (STS) are a rare, heterogeneous tumour group. Radiotherapy improves local control. CT is used to plan radiotherapy, but has poor soft tissue definition. MRI has superior soft tissue definition. Contour variation amongst oncologists is an important factor in treatment failure. This study is the first to directly compare STS tumour contouring using CT vs MRI. METHODS: Planning CT and T 2 weighted MR images of eight patients with STS were distributed to four oncologists. Gross tumour volume was contoured on both imaging modalities using in-house software. Images were recontoured 6 weeks later. The mean distance to agreement (DTA), standard deviation of the DTA, dice similarity coefficient (DSC) and contour volume were calculated for each oncologist and compared to a median contour volume. Results for CT and MRI were compared using a pairwise Student's t-test. RESULTS: When comparing MRI to CT, tumour volumes were significantly smaller, with a difference of 21.4 cm3 across all patients (p = 0.008). There was not a statistically significant difference in the mean distance to agreement or dice similarity coefficient, but the standard deviation of the DTA showed a statistically significant improvement ( p = 0.04). For intraobserver variation, there was no statistically significant improvement using MRI vs CT. CONCLUSION: Oncologists contour smaller tumour volumes using MRI, with reduced interobserver variation. Improving the reliability and consistency of contouring is needed for improved quality assurance. ADVANCES IN KNOWLEDGE: With further experience, the use of MRI in STS radiotherapy planning may reduce variation between oncologists and contribute to improved local control and reduced treatment toxicities.

Changes in prostate apparent diffusion coefficient values during radiotherapy after neoadjuvant hormones.

BACKGROUND: Changes in prostate cancer apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (MRI) provide a noninvasive method for assessing radiotherapy response. This may be attenuated by neoadjuvant hormone therapy (NA-HT). We investigate ADC values measured before, during and after external beam radiotherapy (EBRT) following NA-HT. METHODS: Patients with ⩾T2c biopsy-proven prostate cancer receiving 3 months of NA-HT plus definitive radiotherapy were prospectively identified. All underwent ADC-MRI scans in the week before EBRT, in the third week of EBRT and 8 weeks after its completion. Imaging was performed at 1.5 T. The tumour, peripheral zone (PZ) and central zone (CZ) of the prostate gland were identified and median ADC calculated for each region and time point. RESULTS: Between September and December 2014, 15 patients were enrolled (median age 68.3, range 57-78) with a median Gleason score of 7 (6-9) and prostate-specific antigen (PSA) at diagnosis 14 (3-197) ng/ml. Median period of NA-HT prior to first imaging was 96 days (69-115). All patients completed treatment. Median follow up was 25 months (7-34), with one patient relapsing in this time. Thirteen patients completed all imaging as intended, one withdrew after one scan and another missed the final imaging. PZ and CZ could not be identified in one patient. Median tumour ADC before, during and post radiotherapy was 1.24 × 10-3 mm2/s (interquartile range 0.16 × 10-3 mm2/s), 1.31 × 10-3 mm2/s (0.22 × 10-3 mm2/s), then 1.32 × 10-3 mm2/s (0.13 × 10-3 mm2/s) respectively (p > 0.05). There was no significant difference between median tumour and PZ or CZ ADC at any point. Gleason score did not correlate with ADC values. CONCLUSIONS: Differences in ADC parameters of normal and malignant tissue during EBRT appear attenuated by prior NA-HT. The use of changes in ADC as a predictive tool in this group may have limited utility.

Pre-treatment tumour perfusion parameters and initial RECIST response do not predict long-term survival outcomes for patients with head and neck squamous cell carcinoma treated with induction chemotherapy.

OBJECTIVES: Previously, we showed that pre-treatment tumour plasma perfusion (Fp) predicts RECIST response to induction chemotherapy (ICT) in locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The aim here was to determine whether the pre-treatment tumour Fp estimate, changes in tumour Fp or RECIST response post 2 cycles of ICT were prognostic for long-term survival outcomes. METHODS: A prospective study enrolled patients with high stage HNSCC treated with docetaxel (T), cisplatin (P) and 5-fluorouracil (F) (ICT) followed by synchronous cisplatin and intensity modulated radiotherapy. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before and after two cycles of ICT was used to measure Fp and RECIST response. RESULTS: Forty-two patients were recruited and 37 underwent two scans. The median follow-up was 36 (range 23-49) months. Pre-treatment tumour Fp (stratified by median) was not prognostic for overall survival (p = 0.42), disease specific survival (p = 0.20) and locoregional control (p = 0.64). Neither change in tumour Fp nor RECIST response post two cycles of ICT was prognostic for any outcome (p>0.21). CONCLUSION: DCE-MRI parameters do not predict long-term survival outcomes following ICT and RECIST response to ICT may not be an appropriate endpoint to determine early efficacy of a treatment in HNSCC patients.

Image Guided Radiation Therapy Strategies for Pelvic Lymph Node Irradiation in High-Risk Prostate Cancer: Motion and Margins.

PURPOSE: To quantify the relative motion of the pelvic lymph nodes (LNs), seminal vesicles (SV) and prostate and define indicative margins for image-guided radiotherapy based on bony anatomy or prostate correction strategies for a 3 or 6 degrees-of-freedom couch. METHODS AND MATERIALS: Nineteen patients had a planning computed tomography (CT) scan followed by a mean of 11 repeated CT scans during radiation therapy. The prostate, SV, and external and internal iliac LN regions on the left and right were outlined on each CT scan. Systematic and random uncertainties were determined along with correlations between the motions of these regions. The clinical target volume to planning target volume margins required to take only motion into account were calculated for each guidance method. RESULTS: For bone guidance, motion of the prostate and LNs was largely uncorrelated. Margins to compensate for motion (left-right, superior-inferior, anterior-posterior, in cm) based on a 3-DOF couch were as follows: prostate (0.2, 0.6, 0.8), SV (0.4, 0.9, 1.0), and LNs (0.3, 0.4, 0.6). For prostate guidance, margins were calculated for correlated motion: prostate (0, 0, 0), SV (0.3, 0.5, 0.4), and LNs (0.3, 0.5, 0.9). For a 6-DOF couch, these margins were as follows: prostate (0.2, 0.6, 0.8), SV (0.3, 0.9, 1.0), and LNs (0.3, 0.4, 0.3) for bone guidance. For prostate guidance, margins were as follows: prostate (0, 0, 0), SV (0.2, 0.5, 0.4), and LNs (0.3, 0.6, 0.6). CONCLUSIONS: Image guided radiation therapy based on bony anatomy requires larger prostate and SV margins, and guidance on prostate requires larger LN margins. Neither guidance strategy is optimal, and a combination of the 2 or treatment adaptation after a number of fractions might be preferable. Calculation of the total margin should also include delineation uncertainties.

The prognostic value of dynamic contrast-enhanced MRI contrast agent transfer constant Ktrans in cervical cancer is explained by plasma flow rather than vessel permeability.

BACKGROUND: The microvascular contrast agent transfer constant Ktrans has shown prognostic value in cervical cancer patients treated with chemoradiotherapy. This study aims to determine whether this is explained by the contribution to Ktrans of plasma flow (Fp), vessel permeability surface-area product (PS), or a combination of both. METHODS: Pre-treatment dynamic contrast-enhanced MRI (DCE-MRI) data from 36 patients were analysed using the two-compartment exchange model. Estimates of Fp, PS, Ktrans, and fractional plasma and interstitial volumes (vp and ve) were made and used in univariate and multivariate survival analyses adjusting for clinicopathologic variables tumour stage, nodal status, histological subtype, patient age, tumour volume, and treatment type (chemoradiotherapy vs radiotherapy alone). RESULTS: In univariate analyses, Fp (HR=0.25, P=0.0095) and Ktrans (HR=0.20, P=0.032) were significantly associated with disease-free survival while PS, vp and ve were not. In multivariate analyses adjusting for clinicopathologic variables, Fp and Ktrans significantly increased the accuracy of survival predictions (P=0.0089). CONCLUSIONS: The prognostic value of Ktrans in cervical cancer patients treated with chemoradiotherapy is explained by microvascular plasma flow (Fp) rather than vessel permeability surface-area product (PS).