Health-related quality of life in rural cancer survivors compared with their urban counterparts: a systematic review.

PURPOSE: We conducted a systematic review to describe health-related quality of life (HRQOL) in rural cancer survivors (RCS), and compare HRQOL between RCS and urban cancer survivors (UCS). METHOD: We searched Medline, Embase, CINAHL Plus, and PsycINFO for studies with HRQOL in adult cancer survivors living in rural, regional, remote, and urban areas, who had completed definitive primary cancer treatment, without evidence of residual disease. Where available, we used normative and clinically important values to ascribe meaning to HRQOL data. FINDINGS: Fifteen studies (16 papers) were included. Most were from the US (n = 8) and reported on breast cancer survivors (n = 9). Six HRQOL instruments, collecting data across 16 domains, were used. Three instruments were specific to the survivorship phase. Normative and clinical data were available for 12 studies. Compared with normative populations, RCS had clinically worse physical HRQOL (6/12 studies), better social/family (5/7), and functional (3/6) HRQOL, and there were no differences in emotional or/mental HRQOL (9/12). In six studies with rural-urban comparator groups and normative and clinically important data, RCS and UCS had clinically worse physical (3/6 and 2/6, respectively) and better social/family (3/4 and 2/4 studies, respectively) HRQOL than normative populations. Functional HRQOL was better in RCS (2/4 studies) than UCS and normative populations. In 3/6 studies, there were no clinical differences in emotional or/mental HRQOL between RCS, UCS, and normative populations. CONCLUSION: Overall, HRQOL is not clearly better or worse in RCS than UCS. Future research should include different tumor types, rural residents, and survivorship-specific HRQOL instruments.

Multidisciplinary, multicomponent interventions to reduce frailty among older persons in residents of residential care facilities: a scoping review.

BACKGROUND: Frailty reduction and reversal have been addressed successfully among older populations within community settings. However, these findings may not be applicable to residential care settings, largely due to the complex and multidimensional nature of the condition. Relatively, few attempts at frailty prevention exist in residential settings. This review aims to identify and describe best practice models of care for addressing frailty among older populations in residential care settings. This research also sets out to explore the impact of multidisciplinary health service delivery models on health outcomes such as mortality, hospitalisations, quality of life, falls and frailty. METHODS: A scoping review of the literature was conducted to address the project objectives. Reference lists of included studies, bibliographic databases and the grey literature were systematically searched for literature reporting multidisciplinary, multidimensional models of care for frailty. RESULTS: The scoping review found no interventions that met the inclusion criteria. Of the 704 articles screened, 664 were excluded as not relevant. Forty articles were fully assessed, and while no eligible studies were found, relevant data were extracted from 10 near-eligible studies that reported single disciplines or single dimensions rather than a model of care. The physical, nutritional, medicinal, social and cognitive aspects of the near eligible studies have been discussed as playing a key role in frailty reduction or prevention care models. CONCLUSION: This review has identified a paucity of interventions for addressing and reducing frailty in residential care settings. High-quality studies investigating novel models of care for addressing frailty in residential care facilities are required to address this knowledge gap. Similarly, there is a need to develop and validate appropriate screening and assessment tools for frailty in residential care populations. Health service providers and policy-makers should also increase their awareness of frailty as a dynamic and reversible condition. While age is a non-modifiable predictor of frailty, addressing modifiable factors through comprehensive care models may help manage and prevent the physical, social and financial impacts of frailty in the ageing population.

Striving for humane deaths for laboratory mice: hypobaric hypoxia provides a potential alternative to carbon dioxide exposure.

Killing is often an unavoidable and necessary procedure for laboratory mice involved in scientific research, and providing a humane death is vital for public acceptance. Exposure to carbon dioxide (CO2) gas is the most widely used methodology despite well proven welfare concerns. Consequently, the continued use of CO2 and its globally permitted status in legislation and guidelines presents an ethical dilemma for users. We investigated whether killing with hypobaric hypoxia via gradual decompression was associated with better welfare outcomes for killing laboratory mice. We compared the spontaneous behaviour of mice exposed to CO2, decompression or sham conditions, and used analgesic or anxiolytic interventions to determine their relative welfare impact. Gradual decompression resulted in longer times to unconsciousness and death and the pharmacological interventions support the notion of a minimally negative animal experience, while providing further evidence for pain and anxiety associated with exposure to CO2. Decompression resulted in moderate ear haemorrhage, but our welfare assessment suggests this may happen when mice are unconscious. Hence, gradual decompression could be the basis of significant refinement for killing laboratory mice. Future work should corroborate behaviour with neurobiological markers of loss of consciousness to verify the conscious phase of concern for animal welfare.

Parent use of complementary medicine remedies and services for the management of respiratory tract infection in children: a qualitative study.

BACKGROUND: The use of complementary and alternative medicine (CAM) is increasing globally, in both adults and children. A common condition where CAM is used in children is acute respiratory tract infection (ARTI). However, limited information exists regarding specific CAM modalities used in children, and the factors that influence a parent's decision to use CAM for ARTI in children. This research aimed to address this knowledge gap. METHOD: This research used a qualitative descriptive approach. Parents residing in Greater Melbourne, Australia, who had children aged from 0-12 years, and had used CAM for treating ARTI in their children in the last 12 months, were eligible to participate. Parents' perspectives were captured using individual semi-structured interviews, which were then transcribed verbatim. Data were analysed using content analysis. RESULTS: Twenty-four families were interviewed. Several strategies to improve trustworthiness were implemented. Three themes underpinning the parents' decision to use CAM emerged from the data: safety, internal drivers and external drivers. Parents used a breadth of different treatments, predominantly food as medicine, followed by aromatherapy and other CAM remedies typically found in the kitchen, to manage ARTI in their children. Parents often used both CAM practitioners and mainstream medicine to manage ARTI in their children. While mainstream medicine was typically used to rule out any sinister pathology, CAM was often used as a frontline treatment option, with food as medicine (e.g. soups) dominating. This was due in part to concerns regarding the negative aspects of pharmaceutical use. Parents utilised a diverse range of information sources to inform their decision-making, including friends, families and the internet; traditional sources of research evidence were generally not used. CONCLUSION: Child safety was a major factor influencing a primary carer's decision to utilise CAM for ARTI. The safety and effectiveness of remedies utilised by parents now warrants further investigation.

MSTO1 mutations cause mtDNA depletion, manifesting as muscular dystrophy with cerebellar involvement.

MSTO1 encodes a cytosolic mitochondrial fusion protein, misato homolog 1 or MSTO1. While the full genotype-phenotype spectrum remains to be explored, pathogenic variants in MSTO1 have recently been reported in a small number of patients presenting with a phenotype of cerebellar ataxia, congenital muscle involvement with histologic findings ranging from myopathic to dystrophic and pigmentary retinopathy. The proposed underlying pathogenic mechanism of MSTO1-related disease is suggestive of impaired mitochondrial fusion secondary to a loss of function of MSTO1. Disorders of mitochondrial fusion and fission have been shown to also lead to mitochondrial DNA (mtDNA) depletion, linking them to the mtDNA depletion syndromes, a clinically and genetically diverse class of mitochondrial diseases characterized by a reduction of cellular mtDNA content. However, the consequences of pathogenic variants in MSTO1 on mtDNA maintenance remain poorly understood. We present extensive phenotypic and genetic data from 12 independent families, including 15 new patients harbouring a broad array of bi-allelic MSTO1 pathogenic variants, and we provide functional characterization from seven MSTO1-related disease patient fibroblasts. Bi-allelic loss-of-function variants in MSTO1 manifest clinically with a remarkably consistent phenotype of childhood-onset muscular dystrophy, corticospinal tract dysfunction and early-onset non-progressive cerebellar atrophy. MSTO1 protein was not detectable in the cultured fibroblasts of all seven patients evaluated, suggesting that pathogenic variants result in a loss of protein expression and/or affect protein stability. Consistent with impaired mitochondrial fusion, mitochondrial networks in fibroblasts were found to be fragmented. Furthermore, all fibroblasts were found to have depletion of mtDNA ranging from 30 to 70% along with alterations to mtDNA nucleoids. Our data corroborate the role of MSTO1 as a mitochondrial fusion protein and highlight a previously unrecognized link to mtDNA regulation. As impaired mitochondrial fusion is a recognized cause of mtDNA depletion syndromes, this novel link to mtDNA depletion in patient fibroblasts suggests that MSTO1-deficiency should also be considered a mtDNA depletion syndrome. Thus, we provide mechanistic insight into the disease pathogenesis associated with MSTO1 mutations and further define the clinical spectrum and the natural history of MSTO1-related disease.

The dispersion-brightness relation for fast radio bursts from a wide-field survey.

Despite considerable efforts over the past decade, only 34 fast radio bursts-intense bursts of radio emission from beyond our Galaxy-have been reported1,2. Attempts to understand the population as a whole have been hindered by the highly heterogeneous nature of the searches, which have been conducted with telescopes of different sensitivities, at a range of radio frequencies, and in environments corrupted by different levels of radio-frequency interference from human activity. Searches have been further complicated by uncertain burst positions and brightnesses-a consequence of the transient nature of the sources and the poor angular resolution of the detecting instruments. The discovery of repeating bursts from one source3, and its subsequent localization4 to a dwarf galaxy at a distance of 3.7 billion light years, confirmed that the population of fast radio bursts is located at cosmological distances. However, the nature of the emission remains elusive. Here we report a well controlled, wide-field radio survey for these bursts. We found 20, none of which repeated during follow-up observations between 185-1,097 hours after the initial detections. The sample includes both the nearest and the most energetic bursts detected so far. The survey demonstrates that there is a relationship between burst dispersion and brightness and that the high-fluence bursts are the nearby analogues of the more distant events found in higher-sensitivity, narrower-field surveys5.

Complementary and alternative medicine utilisation for the management of acute respiratory tract infection in children: A systematic review.

INTRODUCTION: As many as one in two children across the globe use complementary and alternative medicine (CAM) to manage a health condition. Despite the high prevalence of use, there is still limited information on the types of CAM used in children, particularly for the management of one of the most common childhood health complaints - acute respiratory tract infection (ARTI). This systematic review was undertaken to address this knowledge gap. METHODS: Eligible studies reporting the use of CAM in children with ARTI were identified using a targeted search of seven electronic databases and the grey literature. Data were extracted using a customised data extraction form and appraised using the McMaster critical review forms for quantitative and qualitative studies. Findings were synthesised in narrative form. RESULTS: The search identified 2261 papers, of which 22 studies were eligible for inclusion. The 22 studies reported the use of 118 distinct CAM interventions for the management of ARTI in children. Most (53%, n = 63) of these interventions represented biologically-based therapies, followed by whole medical systems/alternative medical systems (46%, n = 55). No studies reported the use of energy therapies, or manipulative and body-based methods, or mind-body therapies. CONCLUSION: A diverse range of CAM interventions are used in the management of ARTI in children. These interventions largely represent CAM use in the southern region of Asia - India, Pakistan and Bangladesh. Further research is needed to better understand the types of CAM used among children with ARTI in western countries.

Engaging 'communities': anthropological insights from the West African Ebola epidemic.

The recent Ebola epidemic in West Africa highlights how engaging with the sociocultural dimensions of epidemics is critical to mounting an effective outbreak response. Community engagement was pivotal to ending the epidemic and will be to post-Ebola recovery, health system strengthening and future epidemic preparedness and response. Extensive literatures in the social sciences have emphasized how simple notions of community, which project solidarity onto complex hierarchies and politics, can lead to ineffective policies and unintended consequences at the local level, including doing harm to vulnerable populations. This article reflects on the nature of community engagement during the Ebola epidemic and demonstrates a disjuncture between local realities and what is being imagined in post-Ebola reports about the lessons that need to be learned for the future. We argue that to achieve stated aims of building trust and strengthening outbreak response and health systems, public health institutions need to reorientate their conceptualization of 'the community' and develop ways of working which take complex social and political relationships into account.This article is part of the themed issue 'The 2013-2016 West African Ebola epidemic: data, decision-making and disease control'.

Magnetic Resonance Spectroscopy to Study Glycolytic Metabolism During Autophagy.

Cancer cells undergoing starvation- and treatment-induced autophagy were found to exhibit reduced intracellular lactate, reduced rates of steady-state lactate excretion and reduced real-time pyruvate-lactate exchange rates, indicating that glycolytic metabolism was altered in autophagic cells. In this chapter, we describe the technical details of the use of 1H-magnetic resonance spectroscopy (MRS) to measure endogenous cellular concentrations of lactate and glucose in autophagic cells and tissues, how to measure the rate of steady-state lactate excretion and glucose uptake by 1H-MRS in autophagic cells, and details of the real-time measurement of [1-13C] pyruvate to lactate exchange in autophagic cells by 13C-MRS-DNP (dynamic nuclear polarization).

Extended T2-IVIM model for correction of TE dependence of pseudo-diffusion volume fraction in clinical diffusion-weighted magnetic resonance imaging.

The bi-exponential intravoxel-incoherent-motion (IVIM) model for diffusion-weighted MRI (DWI) fails to account for differential T 2 s in the model compartments, resulting in overestimation of pseudodiffusion fraction f. An extended model, T2-IVIM, allows removal of the confounding echo-time (TE) dependence of f, and provides direct compartment T 2 estimates. Two consented healthy volunteer cohorts (n = 5, 6) underwent DWI comprising multiple TE/b-value combinations (Protocol 1: TE = 62-102 ms, b = 0-250 mm-2s, 30 combinations. Protocol 2: 8 b-values 0-800 mm-2s at TE = 62 ms, with 3 additional b-values 0-50 mm-2s at TE = 80, 100 ms; scanned twice). Data from liver ROIs were fitted with IVIM at individual TEs, and with the T2-IVIM model using all data. Repeat-measures coefficients of variation were assessed for Protocol 2. Conventional IVIM modelling at individual TEs (Protocol 1) demonstrated apparent f increasing with longer TE: 22.4 ± 7% (TE = 62 ms) to 30.7 ± 11% (TE = 102 ms); T2-IVIM model fitting accounted for all data variation. Fitting of Protocol 2 data using T2-IVIM yielded reduced f estimates (IVIM: 27.9 ± 6%, T2-IVIM: 18.3 ± 7%), as well as T 2 = 42.1 ± 7 ms, 77.6 ± 30 ms for true and pseudodiffusion compartments, respectively. A reduced Protocol 2 dataset yielded comparable results in a clinical time frame (11 min). The confounding dependence of IVIM f on TE can be accounted for using additional b/TE images and the extended T2-IVIM model.

Coding and quantification of a facial expression for pain in lambs.

Facial expressions are routinely used to assess pain in humans, particularly those who are non-verbal. Recently, there has been an interest in developing coding systems for facial grimacing in non-human animals, such as rodents, rabbits, horses and sheep. The aims of this preliminary study were to: 1. Qualitatively identify facial feature changes in lambs experiencing pain as a result of tail-docking and compile these changes to create a Lamb Grimace Scale (LGS); 2. Determine whether human observers can use the LGS to differentiate tail-docked lambs from control lambs and differentiate lambs before and after docking; 3. Determine whether changes in facial action units of the LGS can be objectively quantified in lambs before and after docking; 4. Evaluate effects of restraint of lambs on observers' perceptions of pain using the LGS and on quantitative measures of facial action units. By comparing images of lambs before (no pain) and after (pain) tail-docking, the LGS was devised in consultation with scientists experienced in assessing facial expression in other species. The LGS consists of five facial action units: Orbital Tightening, Mouth Features, Nose Features, Cheek Flattening and Ear Posture. The aims of the study were addressed in two experiments. In Experiment I, still images of the faces of restrained lambs were taken from video footage before and after tail-docking (n=4) or sham tail-docking (n=3). These images were scored by a group of five naïve human observers using the LGS. Because lambs were restrained for the duration of the experiment, Ear Posture was not scored. The scores for the images were averaged to provide one value per feature per period and then scores for the four LGS action units were averaged to give one LGS score per lamb per period. In Experiment II, still images of the faces nine lambs were taken before and after tail-docking. Stills were taken when lambs were restrained and unrestrained in each period. A different group of five human observers scored the images from Experiment II. Changes in facial action units were also quantified objectively by a researcher using image measurement software. In both experiments LGS scores were analyzed using a linear MIXED model to evaluate the effects of tail docking on observers' perception of facial expression changes. Kendall's Index of Concordance was used to measure reliability among observers. In Experiment I, human observers were able to use the LGS to differentiate docked lambs from control lambs. LGS scores significantly increased from before to after treatment in docked lambs but not control lambs. In Experiment II there was a significant increase in LGS scores after docking. This was coupled with changes in other validated indicators of pain after docking in the form of pain-related behaviour. Only two components, Mouth Features and Orbital Tightening, showed significant quantitative changes after docking. The direction of these changes agree with the description of these facial action units in the LGS. Restraint affected people's perceptions of pain as well as quantitative measures of LGS components. Freely moving lambs were scored lower using the LGS over both periods and had a significantly smaller eye aperture and smaller nose and ear angles than when they were held. Agreement among observers for LGS scores were fair overall (Experiment I: W=0.60; Experiment II: W=0.66). This preliminary study demonstrates changes in lamb facial expression associated with pain. The results of these experiments should be interpreted with caution due to low lamb numbers.

Validating a robust double-quantum-filtered (1) H MRS lactate measurement method in high-grade brain tumours.

(1) H MRS measurements of lactate are often confounded by overlapping lipid signals. Double-quantum (DQ) filtering eliminates lipid signals and permits single-shot measurements, which avoid subtraction artefacts in moving tissues. This study evaluated a single-voxel-localized DQ filtering method qualitatively and quantitatively for measuring lactate concentrations in the presence of lipid, using high-grade brain tumours in which the results could be compared with standard acquisition as a reference. Paired standard acquisition and DQ-filtered (1) H MR spectra were acquired at 3T from patients receiving treatment for glioblastoma, using fLASER (localization by adiabatic selective refocusing using frequency offset corrected inversion pulses) single-voxel localization. Data were acquired from 2 × 2 × 2 cm(3) voxels, with a repetition time of 1 s and 128 averages (standard acquisition) or 256 averages (DQ-filtered acquisition), requiring 2.15 and 4.3 min respectively. Of 37 evaluated data pairs, 20 cases (54%) had measureable lactate (fitted Cramér-Rao lower bounds ≤ 20%) in either the DQ-filtered or the standard acquisition spectra. The measured DQ-filtered lactate signal was consistently downfield of lipid (1.33 ± 0.03 ppm vs 1.22 ± 0.08 ppm; p = 0.002), showing that it was not caused by lipid breakthrough, and that it matched the lactate signal seen in standard measurements (1.36 ± 0.02 ppm). In the absence of lipid, similar lactate concentrations were measured by the two methods (mean ratio DQ filtered/standard acquisition = 1.10 ± 0.21). In 7/20 cases with measurable lactate, signal was not measureable in the standard acquisition owing to lipid overlap but was quantified in the DQ-filtered acquisition. Conversely, lactate was undetected in seven DQ-filtered acquisitions but visible using the standard acquisition. In conclusion, the DQ filtering method has proven robust in eliminating lipid and permits uncontaminated measurement of lactate. This is important validation prior to use in tissues outside the brain, which contain large amounts of lipid and which are often susceptible to motion.

Effects of acute chemotherapy-induced mucositis on spontaneous behaviour and the grimace scale in laboratory rats.

Intestinal mucositis is a frequent side-effect of chemotherapy treatment. Many oncological research programs aim to identify novel treatments for this distressing condition, and these programs frequently use rat models. Little is known about the presence and progression of pain in these models and how this can best be treated by analgesic therapy. We used a number of behaviour-based methods of pain assessment to determine which tools were best suited for pain identification. Baseline measures for behavioural assessment, rat grimace score and sociability were determined through analysis of continuously recorded video data and an applied social interaction test (n = 16). Mucositis was then induced by intraperitoneal injection of 5-fluorouracil (150 mg/kg) and further behavioural analyses undertaken. An assessment of enrichment interaction was also made by determining the mass of a plastic chew toy gnawed both pre- and post-chemotherapy injection. Behavioural scoring was performed 1, 6, 12, 24 and 48 h after injection, with facial expression being scored at the 12, 24 and 48 h time-points. Sociability testing was performed once during the post-injection period. No significant differences were found in grimace scores between baseline and later daily measures. Behaviours similar to those previously reported post-laparotomy were observed. Writhing, twitching and back-arching behaviours were most evident in rats affected by mucositis and were increased in frequency (respective P values: 0.002, 0.004 and 0.008) 48 h after chemotherapy injection compared with baseline, implying that pain onset occurred around this time-point. Social investigatory behaviour was also increased (P = 0.002) following disease onset. Each day, rats post-5FU injection gnawed a greater percentage of their Nylabone enrichment by weight than the saline-injected control rats (P = 0.046). These data suggest that, of the tools tested, behavioural assessment scoring may find greatest utility in rodent models of intestinal mucositis and should be investigated further.

TPM3 deletions cause a hypercontractile congenital muscle stiffness phenotype.

OBJECTIVE: Mutations in TPM3, encoding Tpm3.12, cause a clinically and histopathologically diverse group of myopathies characterized by muscle weakness. We report two patients with novel de novo Tpm3.12 single glutamic acid deletions at positions ΔE218 and ΔE224, resulting in a significant hypercontractile phenotype with congenital muscle stiffness, rather than weakness, and respiratory failure in one patient. METHODS: The effect of the Tpm3.12 deletions on the contractile properties in dissected patient myofibers was measured. We used quantitative in vitro motility assay to measure Ca(2+) sensitivity of thin filaments reconstituted with recombinant Tpm3.12 ΔE218 and ΔE224. RESULTS: Contractility studies on permeabilized myofibers demonstrated reduced maximal active tension from both patients with increased Ca(2+) sensitivity and altered cross-bridge cycling kinetics in ΔE224 fibers. In vitro motility studies showed a two-fold increase in Ca(2+) sensitivity of the fraction of filaments motile and the filament sliding velocity concentrations for both mutations. INTERPRETATION: These data indicate that Tpm3.12 deletions ΔE218 and ΔE224 result in increased Ca(2+) sensitivity of the troponin-tropomyosin complex, resulting in abnormally active interaction of the actin and myosin complex. Both mutations are located in the charged motifs of the actin-binding residues of tropomyosin 3, thus disrupting the electrostatic interactions that facilitate accurate tropomyosin binding with actin necessary to prevent the on-state. The mutations destabilize the off-state and result in excessively sensitized excitation-contraction coupling of the contractile apparatus. This work expands the phenotypic spectrum of TPM3-related disease and provides insights into the pathophysiological mechanisms of the actin-tropomyosin complex.

Acquired resistance to EGFR tyrosine kinase inhibitors alters the metabolism of human head and neck squamous carcinoma cells and xenograft tumours.

BACKGROUND: Acquired resistance to molecularly targeted therapeutics is a key challenge in personalised cancer medicine, highlighting the need for identifying the underlying mechanisms and early biomarkers of relapse, in order to guide subsequent patient management. METHODS: Here we use human head and neck squamous cell carcinoma (HNSCC) models and nuclear magnetic resonance (NMR) spectroscopy to assess the metabolic changes that follow acquired resistance to EGFR tyrosine kinase inhibitors (TKIs), and which could serve as potential metabolic biomarkers of drug resistance. RESULTS: Comparison of NMR metabolite profiles obtained from control (CAL(S)) and EGFR TKI-resistant (CAL(R)) cells grown as 2D monolayers, 3D spheroids or xenograft tumours in athymic mice revealed a number of differences between the sensitive and drug-resistant models. In particular, we observed elevated levels of glycerophosphocholine (GPC) in CAL(R) relative to CAL(S) monolayers, spheroids and tumours, independent of the growth rate or environment. In addition, there was an increase in alanine, aspartate and creatine+phosphocreatine in resistant spheroids and xenografts, and increased levels of lactate, branched-chain amino acids and a fall in phosphoethanolamine only in xenografts. The xenograft lactate build-up was associated with an increased expression of the glucose transporter GLUT-1, whereas the rise in GPC was attributed to inhibition of GPC phosphodiesterase. Reduced glycerophosphocholine (GPC) and phosphocholine were observed in a second HNSCC model probably indicative of a different drug resistance mechanism. CONCLUSIONS: Our studies reveal metabolic signatures associated not only with acquired EGFR TKI resistance but also growth pattern, microenvironment and contributing mechanisms in HNSCC models. These findings warrant further investigation as metabolic biomarkers of disease relapse in the clinic.

Use of the temporal median and trimmed mean mitigates effects of respiratory motion in multiple-acquisition abdominal diffusion imaging.

Respiratory motion commonly confounds abdominal diffusion-weighted magnetic resonance imaging, where averaging of successive samples at different parts of the respiratory cycle, performed in the scanner, manifests the motion as blurring of tissue boundaries and structural features and can introduce bias into calculated diffusion metrics. Storing multiple averages separately allows processing using metrics other than the mean; in this prospective volunteer study, median and trimmed mean values of signal intensity for each voxel over repeated averages and diffusion-weighting directions are shown to give images with sharper tissue boundaries and structural features for moving tissues, while not compromising non-moving structures. Expert visual scoring of derived diffusion maps is significantly higher for the median than for the mean, with modest improvement from the trimmed mean. Diffusion metrics derived from mono- and bi-exponential diffusion models are comparable for non-moving structures, demonstrating a lack of introduced bias from using the median. The use of the median is a simple and computationally inexpensive alternative to complex and expensive registration algorithms, requiring only additional data storage (and no additional scanning time) while returning visually superior images that will facilitate the appropriate placement of regions-of-interest when analysing abdominal diffusion-weighted magnetic resonance images, for assessment of disease characteristics and treatment response.

Evaluation of lactate detection using selective multiple quantum coherence in phantoms and brain tumours.

Lactate is a product of glucose metabolism. In tumour tissues, which exhibit enhanced glycolytic metabolism, lactate signals may be elevated, making lactate a potential useful tumour biomarker. Methods of lactate quantitation are complicated because of overlap between the lactate methyl doublet CH3 resonance and a lipid resonance at 1.3 ppm. This study presents the use of a selective homonuclear multiple quantum coherence transfer sequence (SelMQC-CSI), at 1.5 T, to better quantify lactate in the presence of lipids. Work performed on phantoms showed good lactate detection (49%) and lipid suppression (98%) efficiencies. To evaluate the method in the brain, the sequence was tested on a group of 23 patients with treated brain tumours, either glioma (N=20) or secondary metastases in the brain (N=3). Here it was proved to be of use in determining lactate concentrations in vivo. Lactate was clearly seen in SelMQC spectra of glioma, even in the presence of lipids, with high grade glioma (7.3 ± 1.9 mM, mean ± standard deviation) having higher concentrations than low grade glioma (1.9 ± 1.5 mM, p=0.048). Lactate was not seen in secondary metastases in the brain. SelMQC-CSI is shown to be a useful technique for measuring lactate in tumours whose signals are otherwise contaminated by lipid.

First MRI application of an active breathing coordinator.

A commercial active breathing coordinator (ABC) device, employed to hold respiration at a specific level for a predefined duration, was successfully adapted for magnetic resonance imaging (MRI) use for the first time. Potential effects of the necessary modifications were assessed and taken into account. Automatic MR acquisition during ABC breath holding was achieved. The feasibility of MR-ABC thoracic and abdominal examinations together with the advantages of imaging in repeated ABC-controlled breath holds were demonstrated on healthy volunteers. Five lung cancer patients were imaged under MR-ABC, visually confirming the very good intra-session reproducibility of organ position in images acquired with the same patient positioning as used for computed tomography (CT). Using identical ABC settings, good MR-CT inter-modality registration was achieved. This demonstrates the value of ABC, since application of T1, T2 and diffusion weighted MR sequences provides a wider range of contrast mechanisms and additional diagnostic information compared to CT, thus improving radiotherapy treatment planning and assessment.