Simultaneous Quantification of Bone Edema/Adiposity and Structure in Inflamed Bone Using Chemical Shift-Encoded MRI in Spondyloarthritis

PURPOSE: To evaluate proton density fat fraction (PDFF) and R2* as markers of bone marrow composition and structure in inflamed bone in patients with spondyloarthritis. METHODS: Phantoms containing fat, water, and trabecular bone were constructed with proton density fat fraction (PDFF) and bone mineral density (BMD) values matching those expected in healthy bone marrow and disease states, and scanned using chemical shift-encoded MRI (CSE-MRI) at 3T. Measured PDFF and R2* values in phantoms were compared with reference FF and BMD values. Eight spondyloarthritis patients and 10 controls underwent CSE-MRI of the sacroiliac joints. PDFF and R2* in areas of inflamed bone and fat metaplasia in patients were compared with normal bone marrow in controls. RESULTS: In phantoms, PDFF measurements were accurate over the full range of PDFF and BMD values. R2* measurements were positively associated with BMD but also were influenced by variations in PDFF. In patients, PDFF was reduced in areas of inflammation and increased in fat metaplasia compared to normal marrow. R2* measurements were significantly reduced in areas of fat metaplasia. CONCLUSION: PDFF measurements reflect changes in marrow composition in areas of active inflammation and structural damage and could be used for disease monitoring in spondyloarthritis. R2* measurements may provide additional information bone mineral density but also are influenced by fat content

Quantifying bone structure, micro-architecture, and pathophysiology with MRI

The radiology of bone has been transformed by magnetic resonance imaging, which has the ability to interrogate bone's complex architecture and physiology. New techniques provide information about both the macrostructure and microstructure of bone ranging from micrometre detail to the whole skeleton. Furthermore functional information about bone physiology can be used to detect disease early before structural changes occur. The future of bone imaging is in quantifying the anatomical and functional information to diagnose and monitor disease more precisely. This review explores the state of the art in quantitative MRI bone imaging

Whole Body MRI in Multiple Myeloma: Optimising Image Acquisition and Read Times

Objective: To identify the whole-body MRI (WB-MRI) image type(s) with the highest value for assessment of multiple myeloma, in order to optimise acquisition protocols and read times. Methods: Thirty patients with clinically-suspected MM underwent WB-MRI at 3 Tesla. Unenhanced Dixon images [fat-only (FO) and water-only (WO)], post contrast Dixon [fat-only plus contrast (FOC) and water-only plus contrast (WOC)] and diffusion weighted images (DWI) of the pelvis from all 30 patients were randomised and read by three experienced readers. For each image type, each reader identified and labelled all visible myeloma lesions. Each identified lesion was compared with a composite reference standard achieved by review of a complete imaging dataset by a further experienced consultant radiologist to determine truly positive lesions. Lesion count, true positives, sensitivity, and positive predictive value were determined. Time to read each scan set was recorded. Confidence for a diagnosis of myeloma was scored using a Likert scale. Conspicuity of focal lesions was assessed in terms of percent contrast and contrast to noise ratio (CNR). Results: Lesion count, true positives, sensitivity and confidence scores were significantly higher when compared to other image types for DWI (P<0.0001 to 0.003), followed by WOC (significant for sensitivity (P<0.0001 to 0.004), true positives (P = 0.003 to 0.049) and positive predictive value (P< 0.0001 to 0.006)). There was no statistically significant difference in these metrics between FO and FOC. Percent contrast was highest for WOC (P = 0.001 to 0.005) and contrast to noise ratio (CNR) was highest for DWI (P = 0.03 to 0.05). Reading times were fastest for DWI across all observers (P< 0.0001 to 0.014). Discussion: Observers detected more myeloma lesions on DWI images and WOC images when compared to other image types. We suggest that these image types should be read preferentially by radiologists to improve diagnostic accuracy and reporting efficiency

Exploring precision polymers to fine-tune magnetic resonance imaging properties of iron oxide nanoparticles

The use of bio-polymers as stabilising agents for iron oxide-based negative magnetic resonance imaging (MRI) contrast agents has become popular in recent years, however the wide polydispersity of biologically-derived and commercially available polymers limits the ability to produce truly tuneable and reproducible behaviour, a major challenge in this area. In this work, stable colloids of iron oxide nanoparticles were prepared utilising precision-engineered bio-polymer mimics, poly(2-acrylamido-2-methylpropane sodium sulfonate) (P(AMPS)) polymers, with controlled narrow polydispersity molecular weights, as templating stabilisers. In addition to producing magnetic colloids with excellent MRI contrast capabilities (r2 values reaching 434.2 mM−1 s−1 at 25 °C and 23 MHz, several times higher than similar commercial analogues), variable field relaxometry provided unexpected important insights into the dynamic environment of the hydrated materials, and hence their exceptional MRI behaviour. Thanks to the polymer’s templating backbone and flexible conformation in aqueous suspension, nanocomposites appear to behave as “multi-core” clustered species, enhancing interparticle interactions whilst retaining water diffusion, boosting relaxation properties at low frequency. This clustering behaviour, evidenced by small-angle X-ray scattering, and strong relaxometric response, was fine-tuned using the well-defined molecular weight polymer species with precise iron to polymer ratios. By also showing negligible haemolytic activity, these nanocomposites exhibit considerable potential for MRI diagnostics

A diffusion-based quantification technique for assessment of sacroiliitis in adolescents with enthesitis-related arthritis

OBJECTIVE: To investigate the use of a quantitative diffusion-weighted imaging (DWI) tool for measuring inflammation of the sacroiliac joints (SIJs) in enthesitis-related arthritis (ERA). METHODS: A retrospective study was performed with institutional review board approval. Subjects were adolescents who had undergone MRI of the SIJs since January 2010. 10 patients with a clinical diagnosis of ERA and 10 controls with a clinical diagnosis of mechanical back pain were assessed. Axial T1 weighted, short tau inversion recovery (STIR) and DWI (b-values 0, 50, 100, 300 and 600 mm(2) s(-1)) images were acquired. Apparent diffusion coefficient (ADC) maps were generated using a monoexponential fit. On each of four slices, two to three linear regions-of-interest were placed on each joint. Normalized ADC (nADC) values were defined as joint ADC divided by a reference ADC derived from normal sacral bone. STIR images were scored using a modification of an established technique. The correlation between nADC values and STIR scores was evaluated using Spearman's rank correlation. RESULTS: Mean nADC values were significantly higher in cases than in controls (p = 0.0015). There was a strong correlation between STIR scores and nADC values (R = 0.85). CONCLUSION: ADC values are significantly increased in inflamed SIJs compared with controls. There is a good correlation between this diffusion-based method and STIR scores of inflammation. ADVANCES IN KNOWLEDGE: We have described and provisionally validated a method for quantifying the severity of inflammation in the SIJs in ERA using ADC measurements. This method is quick, is reproducible and could potentially be automated

Fat fraction mapping using magnetic resonance imaging: insight into pathophysiology

Adipose cells have traditionally been viewed as a simple, passive energy storage depot for triglycerides. However, in recent years it has become clear that adipose cells are highly physiologically active and have a multitude of endocrine, metabolic, haematological and immune functions. Changes in the number or size of adipose cells may be directly implicated in disease (for example, in the metabolic syndrome), but may also be linked to other pathological processes such as inflammation, malignant infiltration or infarction. Magnetic resonance imaging (MRI) is ideally suited to the quantification of fat, since most of the acquired signal comes from water and fat protons. Fat fraction (FF, the proportion of the acquired signal derived from fat protons) has therefore emerged as an objective, image-based biomarker of disease. Methods for fat fraction quantification are becoming increasingly available in both research and clinical settings, but these methods vary depending on the scanner, manufacturer, imaging sequence and reconstruction software being used. Careful selection of the imaging method - and correct interpretation - can improve the accuracy of FF measurements, minimize potential confounding factors and maximize clinical utility. Here, we review methods for fat quantification and their strengths and weaknesses, before considering how they can be tailored to specific applications, particularly in the gastrointestinal and musculoskeletal systems. FF quantification is becoming established as a clinical and research tool, and understanding the underlying principles will be helpful to both imaging scientists and clinicians

Cis-effects on gene expression in the human prenatal brain associated with genetic risk for neuropsychiatric disorders

The majority of common risk alleles identified for neuropsychiatric disorders reside in non-coding regions of the genome and are therefore likely to impact gene regulation. However, the genes that are primarily affected and the nature and developmental timing of these effects remain unclear. Given the hypothesised role for early neurodevelopmental processes in these conditions, we here define genetic predictors of gene expression in the human fetal brain with which we perform transcriptome-wide association studies (TWASs) of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, bipolar disorder, major depressive disorder and schizophrenia. We identify prenatal cis-regulatory effects on 63 genes and 166 individual transcripts associated with genetic risk for these conditions. We observe pleiotropic effects of expression predictors for a number of genes and transcripts, including those of decreased DDHD2 expression in association with risk for schizophrenia and bipolar disorder, increased expression of a ST3GAL3 transcript with risk for schizophrenia and ADHD, and increased expression of an XPNPEP3 transcript with risk for schizophrenia, bipolar disorder and major depression. For the protocadherin alpha cluster genes PCDHA7 and PCDHA8, we find that predictors of low expression are associated with risk for major depressive disorder while those of higher expression are associated with risk for schizophrenia. Our findings support a role for altered gene regulation in the prenatal brain in susceptibility to various neuropsychiatric disorders and prioritize potential risk genes for further neurobiological investigation

Female sex but not oestrogen receptor expression predicts survival in advanced gastroesophageal adenocarcinoma—a post-hoc analysis of the go2 trial

Gastroesophageal adenocarcinoma is a disease of older adults that is associated with a very poor prognosis. It is less common and has better outcomes in females. The reason for this is unknown but may relate to signalling via the main oestrogen receptors (ER) α and β. In this study, we sought to investigate this using the GO2 clinical trial patient cohort. GO2 recruited older and/or frail patients with advanced gastroesophageal cancer. Immunohistochemistry was performed on tumour samples from 194 patients. The median age of the population was 76 years (range 52–90), and 25.3% were female. Only one (0.5%) tumour sample was positive for ERα, compared to 70.6% for ERβ expression. There was no survival impact according to ERβ expression level. Female sex and younger age were associated with lower ERβ expression. Female sex was also associated with improved overall survival. To our knowledge, this is the largest study worldwide of ER expression in a cohort of patients with advanced gastroesophageal adenocarcinoma. It is also unique, given the age of the population. We have demonstrated that female sex is associated with better survival outcomes with palliative chemotherapy but that this does not appear to be related to ER IHC expression. The differing ER expression according to age supports the concept of a different disease biology with age

Female Sex but Not Oestrogen Receptor Expression Predicts Survival in Advanced Gastroesophageal Adenocarcinoma—A Post-hoc Analysis of the GO2 Trial

Gastroesophageal adenocarcinoma is a disease of older adults that is associated with a very poor prognosis. It is less common and has better outcomes in females. The reason for this is unknown but may relate to signalling via the main oestrogen receptors (ER) α and β. In this study, we sought to investigate this using the GO2 clinical trial patient cohort. GO2 recruited older and/or frail patients with advanced gastroesophageal cancer. Immunohistochemistry was performed on tumour samples from 194 patients. The median age of the population was 76 years (range 52–90), and 25.3% were female. Only one (0.5%) tumour sample was positive for ERα, compared to 70.6% for ERβ expression. There was no survival impact according to ERβ expression level. Female sex and younger age were associated with lower ERβ expression. Female sex was also associated with improved overall survival. To our knowledge, this is the largest study worldwide of ER expression in a cohort of patients with advanced gastroesophageal adenocarcinoma. It is also unique, given the age of the population. We have demonstrated that female sex is associated with better survival outcomes with palliative chemotherapy but that this does not appear to be related to ER IHC expression. The differing ER expression according to age supports the concept of a different disease biology with age