Search

Parafilaroides decorus, also known as sea lion lungworm, is a metastrongyloid nematode that infects otariid hosts, such as the charismatic California sea lion, Zalophus californianus. P. decorus causes bronchointerstitial pneumonia, respiratory distress, reduced ability to swim, dive and hunt and as a result, increased mortality particularly in young animals. Respiratory disease is a leading cause of stranding and admission to rehabilitation centers on the Pacific coast. Low-coverage genomic sequencing of four P. decorus individuals analyzed through Galaxy's RepeatExplorer identified a novel repeat DNA family we employed to design a sensitive quantitative PCR (qPCR) assay for diagnosing infections from fecal or sputum samples. The assay detects as little as 10 fg of P. decorus DNA and a linear regression model developed using a standard curve can be used to estimate the concentration of P. decorus DNA in a sample, ± 0.015 ng. This knowledge can be leveraged to estimate the level of parasite burden, which can be used to design improved treatments for animals in rehabilitation. Improved treatment of infections will aid in more animals being successfully released back into the wild.

The distinct evolutionary pressures faced by Pinnipeds have likely resulted in strong coevolutionary ties to their parasites (Leidenberger et al., 2007). This study focuses on the phocid seal filarial heartworm species Acanthocheilonema spirocauda. A. spirocauda is known to infect a variety of phocid seals, but does not appear to be restricted to a single host species (Measures et al., 1997; Leidenberger et al., 2007; Lehnert et al., 2015). However, to date, seal heartworm has never been reported in grey seals (Halichoerus grypus) (Measures et al., 1997; Leidenberger et al., 2007; Lehnert et al., 2015). The proposed vector for seal heartworm is Echinophthirius horridus, the seal louse. Seal lice are known to parasitize a wide array of phocid seal species, including the grey seal. With the advent of climate change, disease burden is expected to increase across terrestrial and marine mammals (Harvell et al., 2002). Accordingly, increased prevalence of seal heartworm has recently been reported in harbor seals (Phoca vitulina) (Lehnert et al., 2015). Thus, the need for improved, rapid, and cost-effective diagnostics is urgent. Here we present the first A. spirocauda-specific rapid diagnostic test (a quantitative real-time PCR assay), based on a highly repetitive genomic DNA repeat identified using whole genome sequencing and subsequent bioinformatic analysis. The presence of an insect vector provides the opportunity to develop a multifunctional diagnostic tool that can be used not only to detect the parasite directly from blood or tissue specimens, but also as a molecular xenomonitoring (XM) tool that can be used to assess the epidemiological profile of the parasite by screening the arthropod vector. Using this assay, we provide evidence for the first reported case of seal heartworm in a grey seal. Keywords: Harbor seal, Parasites, Seal heartworm, Acanthocheilonema spirocauda, Real-time PCR, Molecular diagnostics, Xenomonitoring, Genomic repeats

The lemurs of Madagascar are threatened by human activities. We present the first molecular detection of canine heartworm (Dirofilaria immitis) in a wild non-human primate, the mouse lemur (Microcebus rufus). Zoonotic D. immitis infection has been associated with clinical pathology that includes serious and often fatal cardiac and pulmonary reactions. With human encroachment and associated increases in free-roaming dog populations in Madagascar, we examined lemurs for zoonotic canid pathogens. D. immitis presents a new potential conservation threat to lemurs. We highlight the need for wide-ranging and effective interventions, particularly near protected areas, to address this growing conservation issue. Keywords: Madagascar conservation, Pathogen spillover, Mosquito-borne disease, Blood parasite, Canine vector-borne diseases, brown mouse lemur, Microcebus rufus

The use of microfilaricidal drugs for the control of onchocerciasis and lymphatic filariasis (LF) necessitates prolonged yearly dosing. Prospects for elimination or eradication of these diseases would be enhanced by the availability of a macrofilaricidal drug. Flubendazole (FLBZ), a benzimidazole anthelmintic, is an appealing candidate. FLBZ has demonstrated potent macrofilaricidal effects in a number of experimental rodent models and in one human trial. Unfortunately, FLBZ was deemed unsatisfactory for use in mass drug administration campaigns due to its limited oral bioavailability. A new formulation that enables sufficient bioavailability following oral administration could render FLBZ an effective treatment for onchocerciasis and LF. Identification of drug-derived effects is important in ascertaining a dosage regimen which is predicted to be lethal to the parasite in situ. In previous histological studies, exposure to FLBZ induced damage to tissues required for reproduction and survival at pharmacologically relevant concentrations. However, more precise and quantitative indices of drug effects are needed. This study assessed drug effects using a transcriptomic approach to confirm effects observed histologically and to identify genes which were differentially expressed in treated adult female Brugia malayi. Comparative analysis across different concentrations (1 μM and 5 μM) and durations (48 and 120 h) provided an overview of the processes which are affected by FLBZ exposure. Genes with dysregulated expression were consistent with the reproductive effects observed via histology in our previous studies. This study revealed transcriptional changes in genes involved in embryo development. Additionally, significant downregulation was observed in genes encoding cuticle components, which may reflect changes in developing embryos, the adult worm cuticle or both. These data support the hypothesis that FLBZ acts predominantly on rapidly dividing cells, and provides a basis for selecting molecular markers of drug-induced damage which may be of use in predicting efficacious FLBZ regimens.

Summary: Background: Magnetic Resonance (MR) imaging is key for investigation of suspected newborn brain abnormalities. Access is limited in low-resource settings and challenging in infants needing intensive care. Portable ultralow field (ULF) MRI is showing promise in bedside adult brain imaging. Use in infants and children has been limited as brain-tissue composition differences necessitate sequence modification. The aim of this study was to develop neonatal-specific ULF structural sequences and test these across a range of gestational maturities and pathologies to inform future validation studies. Methods: Prospective cohort study within a UK neonatal specialist referral centre. Infants undergoing 3T MRI were recruited for paired ULF (64mT) portable MRI by convenience sampling from the neonatal unit and post-natal ward. Key inclusion criteria: 1) Infants with risk or suspicion of brain abnormality, or 2) preterm and term infants without suspicion of major genetic, chromosomal or neurological abnormality. Exclusions: presence of contra-indication for MR scanning. ULF sequence parameters were optimised for neonatal brain-tissues by iterative and explorative design. Neuroanatomic and pathologic features were compared by unblinded review, informing optimisation of subsequent sequence generations in a step-wise manner. Main outcome: visual identification of healthy and abnormal brain tissues/structures. ULF MR spectroscopy, diffusion, susceptibility weighted imaging, arteriography, and venography require pre-clinical technical development and have not been tested. Findings: Between September 23, 2021 and October 25, 2022, 102 paired scans were acquired in 87 infants; 1.17 paired scans per infant. Median age 9 days, median postmenstrual age 40+2 weeks (range: 31+3–53+4). Infants had a range of intensive care requirements. No adverse events observed. Optimised ULF sequences can visualise key neuroanatomy and brain abnormalities. In finalised neonatal sequences: T2w imaging distinguished grey and white matter (7/7 infants), ventricles (7/7), pituitary tissue (5/7), corpus callosum (7/7) and optic nerves (7/7). Signal congruence was seen within the posterior limb of the internal capsule in 10/11 infants on finalised T1w scans. In addition, brain abnormalities visualised on ULF optimised sequences have similar MR signal patterns to 3T imaging, including injury secondary to infarction (6/6 infants on T2w scans), hypoxia-ischaemia (abnormal signal in basal ganglia, thalami and white matter 2/2 infants on T2w scans, cortical highlighting 1/1 infant on T1w scan), and congenital malformations: polymicrogyria 3/3, absent corpus callosum 2/2, and vermian hypoplasia 3/3 infants on T2w scans. Sequences are susceptible to motion corruption, noise, and ULF artefact. Non-identified pathologies were small or subtle. Interpretation: On unblinded review, optimised portable MR can provide sufficient contrast, signal, and resolution for neuroanatomical identification and detection of a range of clinically important abnormalities. Blinded validation studies are now warranted. Funding: The Bill and Melinda Gates Foundation, the MRC, the Wellcome/EPSRC Centre for Medical Engineering, the MRC Centre for Neurodevelopmental Disorders, and the National Institute for Health Research (NIHR) Biomedical Research Centres based at Guy’s and St Thomas’ and South London & Maudsley NHS Foundation Trusts and King's College London.

Summary: The integration of neuroimaging and transcriptomics data, Imaging Transcriptomics, is becoming increasingly popular but standardized workflows for its implementation are still lacking. We describe the Imaging Transcriptomics toolbox, a new package that implements a full imaging transcriptomics pipeline using a user-friendly, command line interface. This toolbox allows the user to identify patterns of gene expression which correlates with a specific neuroimaging phenotype and perform gene set enrichment analyses to inform the biological interpretation of the findings using up-to-date methods.For complete details on the use and execution of this protocol, please refer to Martins et al. (2021).

Brain health means optimal physiological brain function across the normal life-course. It encompasses not only healthy brain aging but also brain diseases, their diagnosis and treatment. In all these areas, molecular science has advanced our understanding.This multi-disciplinary review combines viewpoints from laboratory science, clinical medicine and the bioscience industry. First, we review the advances that molecular science has brought to brain health in the past twenty years. These include therapeutic antibodies for CNS diseases (multiple sclerosis, Alzheimer disease) and the dramatic introduction of RNA-targeted therapeutics. Second, we highlight areas where greater molecular understanding is needed. Salient examples are the relation of brain structure to cognitive symptoms, and molecular biomarkers for diagnosis, target discovery and testing of interventions. Finally, we speculate on aspects of molecular science that are likely to advance brain health in the next twenty years. These include: cell senescence and chronobiology; gene editing (notably, CRISPR) and RNA targeting (RNA interference, miRNA manipulation); brain-immune interactions; novel drug targets (AQP4, HIF1, Toll-like receptors); and novel chemistry to make new drugs (molecular machines, quantum molecular modelling and “click” chemistry). Early testing of the relationships between molecular pathways and clinical manifestations will drive much-needed breakthroughs in neurology and psychiatry.

Abstract Background Ex-vivo cardiovascular magnetic resonance (CMR) imaging has played an important role in the validation of in-vivo CMR characterization of pathological processes. However, comparison between in-vivo and ex-vivo imaging remains challenging due to shape changes occurring between the two states, which may be non-uniform across the diseased heart. A novel two-step process to facilitate registration between ex-vivo and in-vivo CMR was developed and evaluated in a porcine model of chronic myocardial infarction (MI). Methods Seven weeks after ischemia-reperfusion MI, 12 swine underwent in-vivo CMR imaging with late gadolinium enhancement followed by ex-vivo CMR 1 week later. Five animals comprised the control group, in which ex-vivo imaging was undertaken without any support in the LV cavity, 7 animals comprised the experimental group, in which a two-step registration optimization process was undertaken. The first step involved a heart specific flexible 3D printed scaffold generated from in-vivo CMR, which was used to maintain left ventricular (LV) shape during ex-vivo imaging. In the second step, a non-rigid co-registration algorithm was applied to align in-vivo and ex-vivo data. Tissue dimension changes between in-vivo and ex-vivo imaging were compared between the experimental and control group. In the experimental group, tissue compartment volumes and thickness were compared between in-vivo and ex-vivo data before and after non-rigid registration. The effectiveness of the alignment was assessed quantitatively using the DICE similarity coefficient. Results LV cavity volume changed more in the control group (ratio of cavity volume between ex-vivo and in-vivo imaging in control and experimental group 0.14 vs 0.56, p

Magnetic resonance imaging (MRI) has played an increasingly relevant role in understanding infant, child, and adolescent neurodevelopment, providing new insight into developmental patterns in neurotypical development, as well as those associated with potential psychopathology, learning disorders, and other neurological conditions. In addition, studies have shown the impact of a child's physical and psychosocial environment on developing brain structure and function. A rate-limiting complication in these studies, however, is the high cost and infrastructural requirements of modern MRI systems. High costs mean many neuroimaging studies typically include fewer than 100 individuals and are performed predominately in high resource hospitals and university settings within high income countries (HICs). As a result, our knowledge of brain development, particularly in children who live in lower and middle income countries (LMICs) is relatively limited. Low field systems, with magnetic fields less than 100mT offer the promise of lower scanning costs and wide-spread global adoption, but routine low field pediatric neuroimaging has yet to be demonstrated. Here we present the first pediatric MRI data collected on a low cost and assessable 64mT scanner in children 6 weeks to 16 years of age and replicate brain volumes estimates and developmental trajectories derived from 3T MRI data. While preliminary, these results illustrate the potential of low field imaging as a viable complement to more conventional high field imaging systems, and one that may further enhance our knowledge of neurodevelopment in LMICs where malnutrition, psychosocial adversities, and other environmental exposures may profoundly affect brain maturation.

Repetitive behavior is a core symptom of Autism Spectrum Disorder (ASD) and Obsessive-Compulsive Disorder (OCD), and has been associated with impairments in cognitive control. However, it is unclear how cognitive control and associated neural circuitry relate to the development of repetitive behavior in children with these disorders. In a multicenter, longitudinal study (TACTICS; Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes), the development of cognitive control was assessed during late childhood using a longitudinal fMRI design with a modified stop-signal task in children with ASD or OCD, and typically developing (TD) children (baseline: N = 95 (8-12 y), follow-up: N = 53 (10-14 y), average interval: 1.48 y (sd: 0.36, range: 0.98–2.52 y). Stop-signal reaction time (SSRT) decreased over development, regardless of diagnosis. Repetitive behavior in children with ASD and OCD was not associated with performance on the stop-signal task. There were no whole-brain between-group differences in brain activity, but ROI-analyses showed increases in activity in right precentral gyrus over development for children with OCD. In sum, even though subtle differences were observed in the development of brain activity in children with OCD, overall the findings suggest that the development of cognitive control, as assessed by the stop signal task, is similar to typical in children with ASD and OCD.

Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) show overlapping symptomatology and deficits in inhibitory control, which are associated with altered functioning and glutamatergic signaling in fronto-striatal circuitry. These parameters have never been examined together. The purpose of the current study was to investigate functioning during inhibitory control and its association with fronto-striatal glutamate concentrations across these disorders using a multi-center, longitudinal approach. Adolescents with ASD (n = 24), OCD (n = 15) and controls (n = 35) underwent two magnetic resonance imaging (MRI) sessions with a one-year interval. This included proton magnetic resonance spectroscopy (1H-MRS; n = 74) and functional MRI during an inhibitory control task (n = 53). We investigated 1H-MRS data and fMRI data separately as well as integrated in a multimodal analysis using linear models focusing on diagnosis and continuous measures of overlapping compulsivity symptoms. ACC glutamate was reduced over time in the ASD group compared with controls, while striatal glutamate decreased over time independent of diagnosis. Increased compulsive behavior seemed to be associated with increased striatal activity during failed inhibitory control. The integrated analyses showed differential involvement of increased striatal glutamate during failed but decreased striatal glutamate during successful inhibitory control in the OCD group compared to controls and ASD, suggesting different underlying mechanisms for OCD compared to ASD.

Fathers play a crucial role in their children’s socio-emotional and cognitive development. A plausible intermediate phenotype underlying this association is father’s impact on infant brain. However, research on the association between paternal caregiving and child brain biology is scarce, particularly during infancy. Thus, we used magnetic resonance imaging (MRI) to investigate the relationship between observed father–infant interactions, specifically paternal sensitivity, and regional brain volumes in a community sample of 3-to-6-month-old infants (N = 28). We controlled for maternal sensitivity and examined the moderating role of infant communication on this relationship. T2-weighted MR images were acquired from infants during natural sleep. Higher levels of paternal sensitivity were associated with smaller cerebellar volumes in infants with high communication levels. In contrast, paternal sensitivity was not associated with subcortical grey matter volumes in the whole sample, and this was similar in infants with both high and low communication levels. This preliminary study provides the first evidence for an association between father-child interactions and variation in infant brain anatomy. Keywords: Fathers, Father-infant interactions, Infant brain volume, MRI, Infancy, Paternal sensitivity

Abstract Background Cardiovascular magnetic resonance (CMR) imaging may be used to visualize post-ablation atrial scar (PAAS), and three-dimensional late gadolinium enhancement (3D LGE) is the most widely employed technique for imaging of chronic scar. Detection of PAAS provides a unique non-invasive insight into the effects of the ablation and may help guide further ablation procedures. However, there is evidence that PAAS is often not detected by CMR, implying a significant sensitivity problem, and imaging parameters vary between leading centres. Therefore, there is a need to establish the optimal imaging parameters to detect PAAS. Methods Forty subjects undergoing their first pulmonary vein isolation procedure for AF had detailed CMR assessment of atrial scar: one scan pre-ablation, and two scans post-ablation at 3 months (separated by 48 h). Each scan session included ECG- and respiratory-navigated 3D LGE acquisition at 10, 20 and 30 min post injection of a gadolinium-based contrast agent (GBCA). The first post-procedural scan was performed on a 1.5 T scanner with standard acquisition parameters, including double dose (0.2 mmol/kg) Gadovist and 4 mm slice thickness. Ten patients subsequently underwent identical scan as controls, and the other 30 underwent imaging with a reduced, single, dose GBCA (n = 10), half slice thickness (n = 10) or on a 3 T scanner (n = 10). Apparent signal-to-noise (aSNR), contrast-to-noise (aCNR) and imaging quality (Likert Scale, 3 independent observers) were assessed. PAAS location and area (%PAAS scar) were assessed following manual segmentation. Atrial shells with standardised %PAAS at each timepoint were then compared to ablation lesion locations to assess quality of scar delineation. Results A total of 271 3D acquisitions (out of maximum 280, 96.7%) were acquired. Likert scale of imaging quality had high interobserver and intraobserver intraclass correlation coefficients (0.89 and 0.96 respectively), and showed lower overall imaging quality on 3 T and at half-slice thickness. aCNR, and quality of scar delineation increased significantly with time. aCNR was higher with reduced, single, dose of GBCA (p = 0.005). Conclusion 3D LGE CMR atrial scar imaging, as assessed qualitatively and quantitatively, improves with time from GBCA administration, with some indices continuing to improve from 20 to 30 min. Imaging should be performed at least 20 min post-GBCA injection, and a single dose of contrast should be considered. Trial registration Trial registry- United Kingdom National Research Ethics Service 08/H0802/68 – 30th September 2008.

Abstract Background Cardiovascular magnetic resonance (CMR) imaging has been used to visualise post-ablation atrial scar (PAAS), generally employing a three-dimensional (3D) late gadolinium enhancement (LGE) technique. However the reproducibility of PAAS imaging has not been determined. This cross-over study is the first to investigate the reproducibility of the technique, crucial for both future research design and clinical implementation. Methods Forty subjects undergoing first time ablation for atrial fibrillation (AF) had detailed CMR assessment of PAAS. Following baseline pre-ablation scan, two scans (separated by 48 h) were performed at three months post-ablation. Each scan session included 3D LGE acquisition at 10, 20 and 30 min post administration of gadolinium-based contrast agent (GBCA). Subjects were allocated at second scan post-ablation to identical imaging parameters (‘Repro’, n = 10), 3 T scanner (‘3 T’, n = 10), half-slice thickness (‘Half-slice’, n = 10) or half GBCA dose (‘Half-gad’, n = 10). PAAS was compared to baseline scar and then reproducibility was assessed for two measures of thresholded scar (% left atrial (LA) occupied by PAAS (%LA PAAS) and Pulmonary Vein Encirclement (PVE)), and then four measures of non-thresholded scar (point-by-point assessment of PAAS, four normalisation methods). Thresholded measures of PAAS were evaluated against procedural outcome (AF recurrence). Results A total of 271 3D acquisitions (out of maximum 280, 96.7%) were acquired. At 20 and 30 min, inter-scan reproducibility was good to excellent (coefficient of variation at 20 min and 30 min: %LA PAAS 0.41 and 0.20; PVE 0.13 and 0.04 respectively for ‘Repro’ group). Changes in imaging parameters, especially reduced GBCA dose, reduced inter-scan reproducibility, but for most measures remained good to excellent (ICC for %LA PAAS 0.454–0.825, PVE 0.618–0.809 at 30 min). For non-thresholded scar, highest reproducibility was observed using blood pool z-score normalisation technique: inter-scan ICC 0.759 (absolute agreement, ‘Repro’ group). There was no significant relationship between indices of PAAS and AF recurrence. Conclusion PAAS imaging is a reproducible finding. Imaging should be performed at least 20 min post-GBCA injection, and a blood pool z-score should be considered for normalisation of signal intensities. The clinical implications of these findings remain to be established in the absence of a simple correlation with arrhythmia outcome. Trial registration United Kingdom National Research Ethics Service 08/H0802/68 – 30th September 2008.

Cognitive behavioural therapy for psychosis (CBTp) involves helping patients to understand and reframe threatening appraisals of their psychotic experiences to reduce distress and increase functioning. Whilst CBTp is effective for many, it is not effective for all patients and the factors predicting a good outcome remain poorly understood. Machine learning is a powerful approach that allows new predictors to be identified in a data-driven way, which can inform understanding of the mechanisms underlying therapeutic interventions, and ultimately make predictions about symptom improvement at the individual patient level. Thirty-eight patients with a diagnosis of schizophrenia completed a social affect task during functional MRI. Multivariate pattern analysis assessed whether treatment response in those receiving CBTp (n = 22) could be predicted by pre-therapy neural responses to facial affect that was either threat-related (ambiguous ‘neutral’ faces perceived as threatening in psychosis, in addition to angry and fearful faces) or prosocial (happy faces). The models predicted improvement in psychotic (r = 0.63, p = 0.003) and affective (r = 0.31, p = 0.05) symptoms following CBTp, but not in the treatment-as-usual group (n = 16). Psychotic symptom improvement was predicted by neural responses to threat-related affect across sensorimotor and frontal-limbic regions, whereas affective symptom improvement was predicted by neural responses to fearful faces only as well as prosocial affect across sensorimotor and frontal regions. These findings suggest that CBTp most likely improves psychotic and affective symptoms in those endorsing more threatening appraisals and mood-congruent processing biases, respectively, which are explored and reframed as part of the therapy. This study improves our understanding of the neurobiology of treatment response and provides a foundation that will hopefully lead to greater precision and tailoring of the interventions offered to patients. Keywords: Schizophrenia, Cognitive behavioural therapy, Affective processing, Neuroimaging, Positive psychotic symptoms, Depressive symptoms

Assessing the impact of genomic alterations on protein networks is fundamental in identifying the mechanisms that shape cancer heterogeneity. We have used isobaric labeling to characterize the proteomic landscapes of 50 colorectal cancer cell lines and to decipher the functional consequences of somatic genomic variants. The robust quantification of over 9,000 proteins and 11,000 phosphopeptides on average enabled the de novo construction of a functional protein correlation network, which ultimately exposed the collateral effects of mutations on protein complexes. CRISPR-cas9 deletion of key chromatin modifiers confirmed that the consequences of genomic alterations can propagate through protein interactions in a transcript-independent manner. Lastly, we leveraged the quantified proteome to perform unsupervised classification of the cell lines and to build predictive models of drug response in colorectal cancer. Overall, we provide a deep integrative view of the functional network and the molecular structure underlying the heterogeneity of colorectal cancer cells.

Repetitive behaviors are among the core symptoms of both Autism Spectrum Disorder (ASD) and Obsessive-Compulsive Disorder (OCD) and are thought to be associated with impairments in cognitive control. However, it is still unknown how deficits in cognitive control and associated neural circuitry relate to the quality or severity of repetitive behavior in children with these disorders. Therefore, we investigated the behavioral and neural correlates of cognitive control using a modified stop-signal task in a multicenter study of children (aged 8–12 years) with ASD, OCD and typically developing (TD) children (N = 95). As both ASD and OCD have high levels of comorbidity with Attention Deficit/Hyperactivity Disorder (ADHD), we did an exploratory analysis addressing ADHD-symptoms. We found that children with ASD and OCD did not show deficits in cognitive control or changes in brain activity in task-relevant neural networks when compared to TD children. However, increased activity in prefrontal brain areas was associated with increased symptoms of comorbid ADHD. As such, this study does not support differences in cognitive control or associated neural circuitry in children with ASD and OCD, but rather suggests that changes in cognitive control in these disorders may be related to symptoms of comorbid ADHD. Keywords: Autism spectrum disorder, Obsessive-compulsive disorder, Compulsive behavior, Cognitive control, Attention deficit/hyperactivity disorder, fMRI

Objectives: Conventional magnetic resonance imaging (MRI) is used to diagnose and monitor inflammatory disease in relapsing remitting (RR) multiple sclerosis (MS). In the less common primary progressive (PP) form of MS, in which focal inflammation is less evident, biomarkers are still needed to enable evaluation of novel therapies in clinical trials. Our objective was to characterize the association — across the brain and cervical spinal cord — between clinical disability measures in PPMS and two potential biomarkers (one for myelin, and one for atrophy, both resulting from the same imaging technique). Methods: Multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) MRI of the brain and cervical spinal cord were obtained for 15 PPMS patients and 11 matched controls. Data were analysed to estimate the signal related to myelin water (VFM), as well as volume measurements. MS disability was assessed using the Multiple Sclerosis Functional Composite score, which includes measures of cognitive processing (Paced Auditory Serial Addition Test), manual dexterity (9-Hole Peg Test) and ambulatory function (Timed 25-Foot Walk); and the Expanded Disability Status Scale. Results: Brain and spinal cord volumes were different in PPMS compared to controls, particularly ventricular (+46%, p = 0.0006) and cervical spinal cord volume (−16%, p = 0.0001). Brain and spinal cord myelin (VFM) were also reduced in PPMS (brain: −11%, p = 0.01; spine: −19%, p = 0.000004). Cognitive processing correlated with brain ventricular volume (p = 0.009). Manual dexterity correlated with brain ventricular volume (p = 0.007), and both brain and spinal cord VFM (p = 0.01 and 0.06, respectively). Ambulation correlated with spinal cord volume (p = 0.04) and spinal cord VFM (p = 0.04). Interpretation: In this study we demonstrated that mcDESPOT can be used to measure myelin and atrophy in the brain and spinal cord. Results correlate well with clinical disability scores in PPMS representing cognitive, fine motor and ambulatory disability.