Diagnostic utility of 11 C-methionine PET/CT in primary hyperparathyroidism in a UK cohort: A single-centre experience and literature review.

OBJECTIVE: Primary hyperparathyroidism is a common endocrine disorder, with 80% of all cases usually caused by one single hyperfunctioning parathyroid adenoma. Conventional imaging modalities for the diagnostic work-up of primary hyperparathyroidism (PHPT) include ultrasound of the neck, 99mTc-sestamibi scintigraphy, and four-dimensional computed tomography (4D-CT). However, the role of other imaging modalities, such as 11C-methionine PET/CT, in the care pathway for PHPT is currently unclear. Here, we report our experience of the diagnostic utility of 11C-methionine PET/CT in a single-center patient cohort (n = 45). DESIGN: Retrospective single-center cohort study. PATIENTS AND MEASUREMENTS: The data of eligible patients that underwent 11C-methionine PET/CT between 2014 and 2022 at Addenbrooke's Hospital (Cambridge, UK) were collected and analyzed. The clinical utility of imaging modalities was determined by comparing the imaging result with histopathological and biochemical outcomes following surgery. RESULTS: In patients with persistent primary hyperparathyroidism following previous surgery, 11C-methionine PET/CT identified a candidate lesion in 6 of 10 patients (60.0%), and histologically confirmed in 5 (50.0%). 11C-methionine PET/CT also correctly identified a parathyroid adenoma in 9 out of 12 patients (75.0%) that failed to be localized on other imaging modalities. 11C-methionine PET/CT had a sensitivity of 70.0% (95% CI 55.8 - 84.2%) for the detection of parathyroid adenomas. CONCLUSIONS: This study highlights a diagnostic role for 11C-methionine PET/CT in patients that have undergone unsuccessful prior surgery or have equivocal or negative prior imaging results, aiding localization and a targeted surgical approach.

Optoacoustic Imaging Detects Hormone-Related Physiological Changes of Breast Parenchyma.

PURPOSE: Optoacoustic imaging with ultrasound (OPUS) can assess in-vivo perfusion/oxygenation through surrogate measures of oxy, deoxy and total hemoglobin content in tissues. The primary aim of our study was to evaluate the ability of OPUS to detect physiological changes in the breast during the menstrual cycle and to determine qualitative/quantitative metrics of normal parenchymal tissue in pre-/post-menopausal women. The secondary aim was to assess the technique's repeatability. MATERIALS AND METHODS: We performed a prospective ethically approved study in volunteers using OPUS (700, 800 and 850 nm wavelengths) in the proliferative/follicular and secretory phase of the menstrual cycle. Regions of interest (ROIs) were drawn on the most superficial region of fibroglandular tissue and same-day intra-observer repeatability was assessed. We used t-tests to interrogate differences in the OPUS measurements due to hormonal changes and interclass correlation coefficients/Bland-Altman plots to evaluate the repeatability of mean ROI signal intensities. RESULTS: 22 pre-menopausal and 8 post-menopausal volunteers were recruited. 21 participants underwent repeatability examinations. OPUS intensity values were significantly higher (p < 0.0001) at all excitation wavelengths in the secretory compared to the proliferative/follicular phase. Post-menopausal volunteers showed similar optoacoustic values to the proliferative/follicular phase of pre-menopausal volunteers. The repeatability of the technique was comparable to other handheld ultrasound modalities. CONCLUSION: OPUS detects changes in perfusion/vascularity related to the menstrual cycle and menopausal status of breast parenchyma.

Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study.

BACKGROUND: Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic TP53 mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP). METHODS AND FINDINGS: We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific TP53 assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The TP53 mutant allele fraction (TP53MAF) was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP. The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%-22%) compared to 0.7% (IQR 0.3%-2.0%) for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson r = 0.59, p < 0.001), and this correlation improved when patients with ascites were excluded (r = 0.82). The ratio of TP53MAF to volume of disease was higher in relapsed patients (0.04% per cm3) than in untreated patients (0.0008% per cm3, p = 0.004). In nearly all relapsed patients with disease volume > 32 cm3, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to chemotherapy was seen earlier with ctDNA, with a median time to nadir of 37 d (IQR 28-54) compared with a median time to nadir of 84 d (IQR 42-116) for CA-125. In 32 relapsed treatment courses evaluable for response after one cycle of chemotherapy, a decrease in TP53MAF of >60% was an independent predictor of TTP in multivariable analysis (hazard ratio 0.22, 95% CI 0.07-0.67, p = 0.008). Conversely, a decrease in TP53MAF of ≤60% was associated with poor response and identified cases with TTP < 6 mo with 71% sensitivity (95% CI 42%-92%) and 88% specificity (95% CI 64%-99%). Specificity was improved when patients with recent drainage of ascites were excluded. Ascites drainage led to a reduction of TP53MAF concentration. The limitations of this study include retrospective design, small sample size, and heterogeneity of treatment within the cohort. CONCLUSIONS: In this retrospective study, we demonstrated that ctDNA is correlated with volume of disease at the start of treatment in women with HGSOC and that a decrease of ≤60% in TP53MAF after one cycle of chemotherapy was associated with shorter TTP. These results provide evidence that ctDNA has the potential to be a highly specific early molecular response marker in HGSOC and warrants further investigation in larger cohorts receiving uniform treatment.

Grade 3 invasive breast cancer masquerading as a haematoma - the importance of concordance in the clinical and imaging pathway.

Cystic lesions of the breast are an everyday encounter in the symptomatic breast clinic. While the vast majority of cystic lesions are benign, it is important to be aware of the imaging manifestations that indicate a sinister pathology and the pitfalls of biopsy in a complex cystic lesion which make the diagnosis challenging. We present a case of cystic Grade 3 breast cancer and highlight the imaging characteristics and clinicoradiological concordance that achieved the correct diagnosis.

Evaluation of depth of myometrial invasion and overall staging in endometrial cancer: comparison of diffusion-weighted and dynamic contrast-enhanced MR imaging.

PURPOSE: To compare the diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging with that of dynamic contrast material-enhanced (DCE) MR imaging in evaluating the depth of myometrial invasion and overall stage in patients with endometrial cancer. MATERIALS AND METHODS: The institutional review board approved this retrospective study; patient consent was not required. From May 2008 to February 2010, 48 women with endometrial cancer underwent preoperative MR imaging, including T1- and T2-weighted imaging, DW MR imaging (b=0 and 800 sec/mm2) and DCE MR imaging. Two radiologists independently interpreted the depth of myometrial invasion, overall stage, and presence of pitfalls associated with inaccurate assessment of myometrial invasion at T1- and T2-weighted imaging, DW MR imaging, and DCE MR imaging. Myometrial invasion and overall stage were compared by using the McNemar test, and κ statistics were used for reader agreement. RESULTS: For assessing the depth of myometrial invasion, diagnostic accuracy, sensitivity, and specificity, respectively, were as follows: DW MR imaging-reader 1, 90%, 84%, and 100%; reader 2, 85%, 84%, and 88%; DCE MR imaging-reader 1, 71%, 61%, and 88%; reader 2, 79%, 77%, and 82%. The improvement in diagnostic accuracy for reader 1 was significant (P=.035). For myometrial invasion, κ values were 0.75 with DW MR imaging and 0.26 with DCE MR imaging. There was no association between inaccurate assessment of myometrial invasion and standard pitfalls with DW MR imaging. Readers 1 and 2 correctly staged more patients by using DW MR imaging (39 and 38 patients, respectively) than by using DCE MR imaging (29 and 30 patients, respectively) (P<.05). For overall stage, κ values were 0.74 with DW MR imaging and 0.22 with DCE MR imaging. CONCLUSION: DW MR imaging has superior diagnostic accuracy in the assessment of myometrial invasion and significantly higher staging accuracy compared with DCE MR imaging.

Diagnosis and management of breast implant capsule recurrence following mastectomy and subpectoral implant - innovative use of ADM for reconstruction.

It is well reported that patients who have undergone breast augmentation and subsequently develop breast cancer can successfully undergo breast-conserving therapy with preservation of their implants. However, there is a paucity of literature on the radiological investigations and surgical techniques in postmastectomy implant-reconstructed patients who develop recurrences to enable preservation of their implant-based reconstruction whilst effectively treating the local recurrence. The wide adoption of acellular dermal matrix use in prosthetic breast reconstruction in recent years has made radiological evaluation of such patients challenging. Herein presented is a case of a 37-year-old woman where wide local excision of a local recurrence abutting a peri-implant capsule following previous mastectomy and implant-acellular dermal matrix (ADM) reconstruction was performed with successful preservation of reconstruction volume (and shape) using an ADM patch to repair the capsular defect whilst retaining the implant in situ. Radiological investigation facilitated and guided the surgical planning and oncological clearance.

An Approach to a Patient With Primary Hyperparathyroidism and a Suspected Ectopic Parathyroid Adenoma.

Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia driven by excess parathyroid hormone (PTH) secretion. PHPT is a common endocrine condition with a prevalence of 1 to 7 cases per 1000 adults. PHPT typically presents in the fifth or sixth decade and shows significant female preponderance. Solitary hyperfunctioning parathyroid adenomas account for 85% to 90% of PHPT cases. The remaining 10% to 15% include cases of multiglandular disease (multiple adenomas or hyperplasia) and, rarely, parathyroid carcinoma (1%). Ectopic parathyroid adenomas may arise due to abnormal embryological migration of the parathyroid glands and can be difficult to localize preoperatively, making surgical cure challenging on the first attempt. The potential existence of multiglandular disease should be considered in all patients in whom preoperative localization fails to identify a target adenoma or following unsuccessful parathyroidectomy. Risk factors for multiglandular disease include underlying genetic syndromes (eg, MEN1/2A), lithium therapy, or previous radiotherapy. In addition to multifocal disease, the possibility of an ectopic parathyroid gland should also be considered in patients requiring repeat parathyroid surgery. In this article, we use illustrative clinical vignettes to discuss the approach to a patient with primary hyperparathyroidism (PHPT) and a suspected ectopic parathyroid adenoma.

Magnetization transfer imaging of ovarian cancer: initial experiences of correlation with tissue cellularity and changes following neoadjuvant chemotherapy.

Objectives: To investigate the relationship between magnetization transfer (MT) imaging and tissue macromolecules in high-grade serous ovarian cancer (HGSOC) and whether MT ratio (MTR) changes following neoadjuvant chemotherapy (NACT). Methods: This was a prospective observational study. 12 HGSOC patients were imaged before treatment. MTR was compared to quantified tissue histology and immunohistochemistry. For a subset of patients (n = 5), MT imaging was repeated after NACT. The Shapiro-Wilk test was used to assess for normality of data and Spearman's rank-order or Pearson's correlation tests were then used to compare MTR with tissue quantifications. The Wilcoxon signed-rank test was used to assess for changes in MTR after treatment. Results: Treatment-naïve tumour MTR was 21.9 ± 3.1% (mean ± S.D.). MTR had a positive correlation with cellularity, rho = 0.56 (p < 0.05) and a negative correlation with tumour volume, ρ = -0.72 (p = 0.01). MTR did not correlate with the extracellular proteins, collagen IV or laminin (p = 0.40 and p = 0.90). For those patients imaged before and after NACT, an increase in MTR was observed in each case with mean MTR 20.6 ± 3.1% (median 21.1) pre-treatment and 25.6 ± 3.4% (median 26.5) post-treatment (p = 0.06). Conclusion: In treatment-naïve HGSOC, MTR is associated with cellularity, possibly reflecting intracellular macromolecular concentration. MT may also detect the HGSOC response to NACT, however larger studies are required to validate this finding. Advances in knowledge: MTR in HGSOC is influenced by cellularity. This may be applied to assess for cell changes following treatment.

T1-weighted fat-suppressed imaging of the pelvis with a dual-echo Dixon technique: initial clinical experience.

PURPOSE: To compare the image quality of water-only images generated from a dual-echo Dixon technique with that of standard fast spin-echo T1-weighted chemical shift fat-suppressed images obtained in patients evaluated for pelvic pain with a 1.5-T magnetic resonance (MR) system. MATERIALS AND METHODS: The ethics board granted approval for this retrospective study; patient consent was not required. Twenty-five women underwent both standard axial T1-weighted fast spin-echo chemical shift fat-suppressed imaging and dual-echo Dixon imaging of the pelvis. Two readers independently scored the acquisitions for image quality, fat suppression quality, and artifact. On the basis of signal intensity measurements, the uniformity of fat suppression, the contrast between fat-suppressed and non-fat-suppressed tissue, and the contrast between pathologic lesions and suppressed fat were calculated. Values obtained with the T1-weighted fat-suppressed and dual-echo Dixon techniques were compared by using the Wilcoxon signed rank test. RESULTS: The images generated with the dual-echo Dixon technique were of higher quality, had better fat suppression, and had less artifact (qualitative scores: 4.4, 4.6, and 4.0, respectively) compared with the standard T1-weighted fat-suppressed images (qualitative scores: 3.4, 3.3, and 3.6, respectively; P < .01). Contrast between fat-suppressed and non-fat-suppressed tissue (contrast ratio: 0.86 for dual-echo Dixon technique vs 0.42 for T1-weighted fat-suppressed technique, P < .001) and between pathologic lesions and suppressed fat (contrast ratio: 0.88 for dual-echo Dixon technique vs 0.57 for T1-weighted fat-suppressed technique, P =.012) was significantly improved with the dual-echo Dixon technique. Twelve pathologic lesions were identified with dual-echo Dixon imaging versus eight that were identified with T1-weighted fat-suppressed imaging. CONCLUSION: Compared with standard T1-weighted fat-suppressed imaging, dual-echo Dixon imaging facilitates improved image quality of fat-suppressed images of the pelvis, enabling better delineation of pathologic lesions.

Recurrent myoid hamartoma of the breast mimicking malignancy.

Myoid (muscular) hamartoma is a rare form of benign breast hamartoma composed of differentiated mammary glandular and stromal structures, fatty tissue and areas of smooth muscle from which its name originates. It is considered to be a variant of a mammary hamartoma. We report the clinical presentation, imaging appearances and treatment of the initial and recurrent presentation of this rare tumour in a 61year old female, which mimicked malignancy.  Although rare, myoid hamartoma's can reoccur and when they do they imaging appearances of benign and malignant tumours can overlap tend to mimic malignancy and histological diagnosis is mandatory.

Corrigendum to 'Sebaceous carcinoma of the chest wall: A case report' [Radiology Case Reports 16 (2021) 1870-1873].

[This corrects the article DOI: 10.1016/j.radcr.2021.04.060.].

Extravasation of Epirubicin chemotherapy from a port-a-cath causing extensive breast necrosis: Sequential imaging findings and management of a breast cancer patient.

Extravasation of chemotherapy is rare with an estimated incidence of 0.01%-7% but can cause significant morbidity, delay in cancer treatment and potential mortality. We present a case of 55-year-old woman with a metastatic right axillary lymph node with no identifiable breast primary, commenced on chemotherapy as per multidisciplinary team decision. Extravasation of 25 mls of Epirubicin chemotherapy at the porta-a-cath (site) caused extensive inflammatory change in the breast parenchyma and chest wall with a necrotic ulcerating skin-defect. Even with ensuring port or peripheral catheter patency and position, extravasation can occur. This is the first case report to describe the use of MRI to help plan management, identifying the extent of the tissue damage and vascular compromise which could impair healing. In this case the necrotic ulcer was managed with surgical debridement and human ADM matrix (Matriderm dermal matrix) which has not been described in the literature previously.

Nonovarian cystic lesions of the pelvis.

Cystic disease in the female pelvis is common. The majority of cystic pelvic masses originate in the ovary, and they can range from simple, functional cysts to malignant ovarian tumors. Mimics of ovarian cystic masses include peritoneal inclusion cyst, paraovarian cyst, mucocele of the appendix, obstructed fallopian tube (eg, hydrosalpinx, pyosalpinx, and hematosalpinx), uterine leiomyoma, adenomyosis, spinal meningeal cyst, unicornuate uterus, lymphocele, cystic degeneration of lymph nodes, lymphangioleiomyomatosis, hematoma, and abscess. A cystic pelvic mass is nonovarian if it is separate from the normal ovaries. However, the different types of cystic pelvic masses may have similar imaging appearances, and radiologic evaluation may be of limited diagnostic use. It is important to understand the relationship of a mass with its anatomic location, identify normal ovaries at imaging, and relate imaging findings to the patient's clinical history to avoid misdiagnosis.

Pelvic imaging following chemotherapy and radiation therapy for gynecologic malignancies.

Gynecologic malignancies account for 10%-15% of all malignancies in females. A variety of oncologic options are available depending on organ of origin, histologic diagnosis, and disease grade and stage. Gynecologic malignancies are usually treated with surgery, chemotherapy, or radiation therapy. Posttreatment imaging plays a crucial role in the assessment of treatment response and tumor recurrence. Imaging of the female pelvis following chemotherapy and radiation therapy is particularly challenging due to alteration of the normal anatomy and loss of tissue planes. Expected changes in appearance occur following chemotherapy-radiation therapy, as do complications such as fistulas, proctitis, enteritis, typhlitis, cystitis, and insufficiency fractures. Radiologists should be familiar with both the expected posttreatment imaging findings and the imaging features of common complications to help make the correct interpretation and avoid possible pitfalls.

Visceral abdominal obesity--is there an increased prevalence in men presenting with testicular teratoma?

BACKGROUND: There is evidence to suggest a link between the accumulation of visceral abdominal adipose tissue and an increased incidence of prostate, endometrial, breast, and colonic cancer. PURPOSE: To investigate whether an increase in ratio of visceral to subcutaneous abdominal adipose tissue is demonstrated in patients with testicular teratoma. MATERIAL AND METHODS: Following ethical approval, 22 male patients who had undergone staging computed tomography (CT) between 2004 and 2007 for testicular teratoma were identified from our database. Abdominal adipose tissue distribution for these 22 patients was compared with that of 22 control patients, standardized for age, sex, and body mass index. Visceral and subcutaneous adipose tissue volumes were calculated from a single axial CT slice at the level of the umbilicus. A two-sample t test for the difference in volume ratio between the two groups was used. A P value of < 0.05 was considered statistically significant. RESULTS: There was a statistically significant difference in the mean ratio of visceral to subcutaneous volumes between the teratoma patients and controls (P=0.02). The ratio in teratoma patients was 1.56 times greater than seen in control patients. CONCLUSION: Patients with testicular teratoma have a relatively greater proportion of abdominal visceral adipose tissue compared with controls. This is concordant with published literature for other malignancies.

Radiological staging of ovarian carcinoma.

Ovarian cancer is the sixth most commonly diagnosed cancer in the world, accounting for 4% of all female cancers. An estimated 1 in 71 women in the United States will develop ovarian cancer in their lifetime. Accurate staging of ovarian carcinoma is vital in the appropriate management and counseling of patients. The surgical staging proposed by the International Federation of Obstetrics and Gynaecology is the most universally used, and International Federation of Obstetrics and Gynaecology encourages the use of imaging techniques to assess prognostic factors, such as resectable disease and lymph node status. Identifying the volume and locations of tumor is valuable in planning percutaneous tissue biopsy, triaging patients to either primary cytoreductive surgery, or primary platinum-based chemotherapy. Contrast-enhanced computed tomography is the modality of choice for the staging of ovarian carcinoma, with magnetic resonance imaging being used as a problem-solving tool. In this article we discuss and illustrate the staging of ovarian carcinoma, with emphasis on the current imaging modalities and optimal image acquisition.

Achieving margin clearance following oncoplastic breast surgery in comparison with simple wide local excision: a three-dimensional specimen assessment.

BACKGROUND: Pre-operative breast tumour radial dimensions often determine the choice between simple wide local excision (WLE) and oncoplastic breast surgery (OBS). We reviewed the three-dimensional interplay between tumour and surgical specimen dimensions in the two cohorts. METHODS: Demographic, tumour and treatment data were collected for all patients undergoing OBS by a single surgeon and compared with a randomly selected cohort of WLE patients treated. The relationship between tumour and specimen medio-lateral, supero-inferior and antero-posterior dimensions were explored in both groups. Subgroup analyses were performed in the OBS cohort (parenchymal displacement versus replacement). RESULTS: We identified 60 OBS patients (63 breasts), comparing them with 60 WLE patients. Pre-operative tumour estimated size was significantly larger in the OBS cohort and concordant with macroscopic tumour radial dimensions and final microscopic tumour size. Surgical specimen weight was more than 3.5 times higher in the OBS group and its radial dimensions were almost double. No significant difference was observed for the antero-posterior dimensions. The rate of margin re-excisions and completion mastectomies were lower in the OBS cohort. WLE patients with positive margins had a lower tumour-to-specimen ratio, whereas, the requirement for further surgery in the OBS cohort was associated with larger tumour dimensions. CONCLUSION: Despite larger tumour dimensions, OBS is not inferior to WLE in providing clear surgical margins. Our analysis of the three-dimensional spatial relationship between cancer and surgical specimen, although not completely conclusive, can be helpful in the selection of the most appropriate surgical approach for every patient.

Metabolic-flow relationships in primary breast cancer: feasibility of combined PET/dynamic contrast-enhanced CT.

PURPOSE: To assess the feasibility and first experience of combined (18)F-FDG-PET)/dynamic contrast-enhanced (DCE) CT in evaluating breast cancer. METHODS: Nine consecutive female patients (mean age 64.2 years, range 52-74 years) with primary breast carcinoma were prospectively recruited for combined (18)F-FDG PET/DCE-CT. Dynamic CT data were used to calculate a range of parameters of tumour vascularity, and tumour (18)F-FDG uptake (standardized uptake value, SUVmax) was used as a metabolic indicator. RESULTS: One tumour did not enhance and was excluded. The mean tumour SUVmax was 7.7 (range 2.4-26.1). The mean values for tumour perfusion, perfusion normalized to cardiac output, standard perfusion value (SPV) and permeability were 41 ml/min per 100 g (19-59 ml/min per 100 g), 0.56%/100 g (0.33-1.09%/100 g), 3.6 (2.5-5.9) and 0.15/min (0.09-0.30/min), respectively. Linear regression analysis showed a positive correlation between tumour SUV and tumour perfusion normalized to cardiac output (r=0.55, p=0.045) and a marginal correlation between tumour SUV and tumour SPV (r=0.19, p=0.065). There were no significant correlations between tumour SUV and tumour perfusion (r=0.29, p=0.401) or permeability (r=0.03, p=0.682). CONCLUSION: The first data from combined (18)F-FDG-PET/DCE-CT in breast cancer are reported. The technique was successful in eight of nine patients. Breast tumour metabolic and vascular parameters were consistent with previous data from (15)O-H(2)O-PET.

Phenotypic Analysis of Human Lymph Nodes in Subjects With New-Onset Type 1 Diabetes and Healthy Individuals by Flow Cytometry.

Background: Ultrasound guided sampling of human lymph node (LN) combined with advanced flow cytometry allows phenotypic analysis of multiple immune cell subsets. These may provide insights into immune processes and responses to immunotherapies not apparent from analysis of the blood. Methods: Ultrasound guided inguinal LN samples were obtained by both fine needle aspiration (FNA) and core needle biopsy in 10 adults within 8 weeks of diagnosis of type 1 diabetes (T1D) and 12 age-matched healthy controls at two study centers. Peripheral blood mononuclear cells (PBMC) were obtained on the same occasion. Samples were transported same day to the central laboratory and analyzed by multicolour flow cytometry. Results: LN sampling was well-tolerated and yielded sufficient cells for analysis in 95% of cases. We confirmed the segregation of CD69+ cells into LN and the predominance of CD8+ Temra cells in blood previously reported. In addition, we demonstrated clear enrichment of CD8+ naïve, FOXP3+ Treg, class-switched B cells, CD56bright NK cells and plasmacytoid dendritic cells (DC) in LNs as well as CD4+ T cells of the Th2 phenotype and those expressing Helios and Ki67. Conventional NK cells were virtually absent from LNs as were Th22 and Th1Th17 cells. Paired correlation analysis of blood and LN in the same individuals indicated that for many cell subsets, especially those associated with activation: such as CD25+ and proliferating (Ki67+) T cells, activated follicular helper T cells and class-switched B cells, levels in the LN compartment could not be predicted by analysis of blood. We also observed an increase in Th1-like Treg and less proliferating (Ki67+) CD4+ T cells in LN from T1D compared to control LNs, changes which were not reflected in the blood. Conclusions: LN sampling in humans is well-tolerated. We provide the first detailed "roadmap" comparing immune subsets in LN vs. blood emphasizing a role for differentiated effector T cells in the blood and T cell regulation, B cell activation and memory in the LN. For many subsets, frequencies in blood, did not correlate with LN, suggesting that LN sampling would be valuable for monitoring immuno-therapies where these subsets may be impacted.

Sodium MRI with 3D-cones as a measure of tumour cellularity in high grade serous ovarian cancer.

The aim of this study was to assess the feasibility of rapid sodium MRI (23Na-MRI) for the imaging of peritoneal cancer deposits in high grade serous ovarian cancer (HGSOC) and to evaluate the relationship of 23Na-MRI with tumour cellularity. 23Na-MRI was performed at 3 T on twelve HGSOC patients using a 3D-cones acquisition technique. Tumour biopsies specimens were collected after imaging and cellularity was measured from histology. Total 23Na-MRI scan time for each patient was approximately 11 min. At an isotropic resolution of 5.6 mm, signal-to-noise ratios (SNRs) of 82.2 ± 15.3 and 15.1 ± 7.1 (mean ± standard deviation) were achieved for imaging of tumour tissue sodium concentration (TSC) and intracellular weighted sodium concentration (IWS) respectively. Tumour TSC and IWS concentrations were: 56.8 ± 19.1 mM and 30.8 ± 9.2 mM respectively and skeletal muscle TSC and IWS concentrations were 33.2 ± 16.3 mM and 20.5 ± 9.9 mM respectively. There were significant sodium concentration differences between cancer and skeletal muscle, Wilcoxon signed-rank test, P < 0.001 for TSC and P = 0.01 for IWS imaging. Tumour cellularity displayed a strong negative correlation with TSC, Spearman's rho = -0.92, P < 0.001, but did not correlate with IWS. This study demonstrates that 23Na-MRI using 3D-cones can rapidly assess sodium concentration in peritoneal deposits of HGSOC and that TSC may serve as a biomarker of tumour cellularity.