Purpose
To develop a new myelin water imaging (MWI) technique using a short‐TR adiabatic inversion‐recovery (STAIR) sequence on a clinical 3T MR scanner.
Methods
Myelin water (MW) in the brain has ...both a much shorter T1 and a much shorter T2* than intracellular/extracellular water. A STAIR sequence with a short TR was designed to efficiently suppress long T1 signals from intracellular/extracellular water, and therefore allow selective imaging of MW, which has a much shorter T1. Numerical simulation and phantom studies were performed to investigate the effectiveness of long T1 signal suppression. TheT2* in white matter (WM) was measured with STAIR and compared with T2* measured with a conventional gradient recall echo in in vivo study. Four healthy volunteers and 4 patients with multiple sclerosis were recruited for qualitative and quantitative MWI. Apparent MW fraction was generated to compare MW in normal WM in volunteers to MW in lesions in patients with multiple sclerosis.
Results
Both simulation and phantom studies showed that when TR was sufficiently short (eg, 250 ms), the STAIR sequence effectively suppressed long T1 signals from tissues with a broad range of T1s using a single TR/TI combination. The volunteer study showed a short T2* of 9.5 ± 1.7 ms in WM, which is similar to reported values for MW. Lesions in patients with multiple sclerosis showed a significantly lower apparent MW fraction (4.5% ± 1.0%) compared with that of normal WM (9.2% ± 1.5%) in healthy volunteers (p < 0.05).
Conclusions
The STAIR sequence provides selective MWI in brain and can quantify reductions in MW content in patients with multiple sclerosis.
Purpose
Direct myelin imaging can improve the characterization of myelin‐related diseases such as multiple sclerosis. In this study, we explore a novel method to directly image myelin using inversion ...recovery‐prepared hybrid encoding (IR‐HE) UTE MRI.
Methods
The IR‐HE sequence uses an adiabatic inversion pulse to suppress the long T2 white matter signal, followed by 3D dual‐echo HE utilizing both single point imaging and radial frequency encoding, for which the subtraction image between 2 echoes reveals the myelin signal with high contrast. To reduce scan time, it is common to obtain multiple spokes per IR. Here, we invented a novel method to improve the HE, adapted for the multi‐spoke IR imaging—termed interleaved HE—for which single point imaging encoding is interleaved between radial frequency encodings near nulling point to allow more efficient IR‐signal suppression. To evaluate the proposed approach, a computer simulation, myelin phantom experiment, an ex vivo experiment with a cadaveric multiple sclerosis brain, and an in vivo experiment with 8 healthy volunteers and 13 multiple sclerosis patients were performed.
Results
The computer simulation showed that IR‐interleaved HE allows for improved contrast of myelin signal with reduced imaging artifacts. The myelin phantom experiment showed IR‐interleaved HE allows direct imaging of myelin lipid with excellent suppression of water signal. In the ex vivo and in vivo experiments, the proposed method demonstrated highly specific imaging of myelin in white matter of the brain.
Conclusion
IR‐interleaved HE allows for time‐efficient, high‐contrast direct myelin imaging and can detect demyelinated lesions in multiple sclerosis patients.
OBJECTIVES: To examine whether treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) in patients with Alzheimer's disease (AD) results in better cognitive ...function.
DESIGN: Randomized double‐blind placebo‐controlled trial. Participants were randomized to therapeutic CPAP for 6 weeks or placebo CPAP for 3 weeks followed by therapeutic CPAP for 3 weeks.
SETTING: General clinical research center.
PARTICIPANTS: Fifty‐two men and women with mild to moderate AD and OSA.
INTERVENTION: CPAP.
MEASUREMENTS: A complete neuropsychological test battery was administered before treatment and at 3 and at 6 weeks.
RESULTS: A comparison of subjects randomized to 3 weeks of therapeutic versus placebo CPAP suggested no significant improvements in cognition. A comparison of pre‐ and posttreatment neuropsychological test scores after 3 weeks of therapeutic CPAP in both groups showed a significant improvement in cognition. The study was underpowered to make definitive statements about improvements within specific cognitive constructs, although exploratory post hoc examination of change scores for individual tests suggested improvements in episodic verbal learning and memory and some aspects of executive functioning such as cognitive flexibility and mental processing speed.
CONCLUSION: OSA may aggravate cognitive dysfunction in dementia and thus may be a reversible cause of cognitive loss in patients with AD. OSA treatment seems to improve some cognitive functioning. Clinicians who care for patients with AD should consider implementing CPAP treatment when OSA is present.
Purpose
Inversion recovery‐based UTE (IR‐UTE) sequences have been proposed to directly image myelin with extremely short T2∗ (~0.3 ms). In this study, we demonstrate the feasibility of complex echo ...subtraction to improve 3D IR‐UTE imaging of myelin in white matter of the brain in vivo.
Methods
In IR‐UTE imaging, long T2 components in white matter (i.e., water) are suppressed using an adiabatic inversion recovery preparation pulse. Dual echo UTE data acquisition and magnitude echo subtraction are used to suppress the residual white matter and gray matter signals, providing high myelin contrast. Complex echo subtraction may further improve the myelin contrast by reducing the residual long T2 water signal contamination caused by regional T1 variations. To verify the efficacy of the complex subtraction technique, in vivo experiments were performed with 5 non‐symptomatic healthy volunteers and 5 multiple sclerosis patients on a 3T clinical MR system. Signal enhancement between the complex subtraction and the magnitude subtraction was introduced to evaluate the improvement.
Results
The complex subtraction improved myelin contrast over the magnitude subtraction in both healthy and patient groups, with more fine myelin structures being revealed. The foci of the demyelinated lesion were more clearly detected by complex subtraction. An average signal enhancement of up to 135.9% was achieved with the complex subtraction over the magnitude subtraction.
Conclusion
The complex echo subtraction improves 3D IR‐UTE morphologic imaging of myelin in white matter of the brain.
Direct myelin imaging is promising for characterization of multiple sclerosis (MS) brains at diagnosis and in response to therapy. In this study, a 3D inversion recovery‐prepared ultrashort echo time ...cones (IR‐UTE‐Cones) sequence was used for both morphological and quantitative imaging of myelin on a clinical 3 T scanner. Myelin powder phantoms with different myelin concentrations were imaged with the 3D UTE‐Cones sequence and it showed a strong correlation between concentrations and UTE‐Cones signals, demonstrating the ability of the UTE‐Cones sequence to directly image myelin in the brain. Quantitative myelin imaging with multi‐echo IR‐UTE‐Cones sequences show similar T2* values for a D2O‐exchanged myelin phantom (T2* = 0.33 ± 0.04 ms), ex vivo brain specimens (T2* = 0.20 ± 0.04 ms) and in vivo healthy volunteers (T2* = 0.254 ± 0.023 ms), further confirming the feasibility of 3D IR‐UTE‐Cones sequences for direct myelin imaging in vivo. In ex vivo MS brain study, signal loss is observed in MS lesions, which was confirmed with histology. For the in vivo study, the lesions in MS patients also show myelin signal loss using the proposed direct myelin imaging method, demonstrating the clinical potential for MS diagnosis. Furthermore, the measured IR‐UTE‐Cones signal intensities show a significant difference between normal‐appearing white matter in MS patients and normal white matter in volunteers, which cannot be found in clinical used T2‐FLAIR sequences. Thus, the proposed 3D IR‐UTE‐Cones sequence showed clinical potential for MS diagnosis with the capability of direct myelin detection of the whole brain.
Myelin T2* measurement using the proposed inversion recovery‐prepared UTE‐Cones (3D IR‐UTE‐Cones) sequence for a healthy volunteer (a 37‐year‐old male). The IR‐UTE‐Cones sequences with multi‐TEs are shown in (A)‐(D), respectively. A T2* of 0.254 ± 0.023ms was calculated by fitting to a single‐component model (E). T2* maps of myelin in white‐matter regions from four different slices are shown in (F)‐(I).
ABSTRACT
Background
Kinematic measures of handwriting movements are sensitive to mild subclinical motor abnormalities stemming from a wide range of disorders involving the basal ganglia including ...Huntington's disease (HD). Prior research has not investigated handwriting movements in at‐risk individuals in the premanifest stage of HD.
Objectives
The purpose of this study was to examine whether handwriting movement abnormalities are present prior to clinically manifest chorea in HD.
Methods
A total of 38 symptomatic HD, 30 gene‐positive premanifest, and 25 healthy control participants completed handwriting tasks consisting of circles, loops, sentences, and spirals with a noninking pen on a digitizing tablet. Multiple measures of pen stroke kinematics and pressure were measured along with the cognitive and motor status of each participant. Burden of pathology and CAG × age product scores were obtained from each participant with HD.
Results
Participants with HD exhibited significantly longer and more variable stroke durations, decreased handwriting smoothness, and increased and more variable pen pressures when compared with the healthy controls. We found significant positive associations between stroke duration and both burden of pathology and CAG × age product. Results from a discriminant function analysis revealed a 7‐factor model that distinguished premanifest from healthy controls with 85% accuracy. Factors in the model included greater variability in stroke amplitude, velocity and pen pressure, higher levels of pen pressure, longer stroke durations, and lower velocities for combinations of handwritten circles, sentences, and spirals.
Conclusions
These findings support the clinical utility of dynamic measures of handwriting kinematics as a potential early behavioral biomarker in HD.
Spasticity is a common and poorly controlled symptom of multiple sclerosis. Our objective was to determine the short-term effect of smoked cannabis on this symptom.
We conducted a placebo-controlled, ...crossover trial involving adult patients with multiple sclerosis and spasticity. We recruited participants from a regional clinic or by referral from specialists. We randomly assigned participants to either the intervention (smoked cannabis, once daily for three days) or control (identical placebo cigarettes, once daily for three days). Each participant was assessed daily before and after treatment. After a washout interval of 11 days, participants crossed over to the opposite group. Our primary outcome was change in spasticity as measured by patient score on the modified Ashworth scale. Our secondary outcomes included patients' perception of pain (as measured using a visual analogue scale), a timed walk and changes in cognitive function (as measured by patient performance on the Paced Auditory Serial Addition Test), in addition to ratings of fatigue.
Thirty-seven participants were randomized at the start of the study, 30 of whom completed the trial. Treatment with smoked cannabis resulted in a reduction in patient scores on the modified Ashworth scale by an average of 2.74 points more than placebo (p < 0.0001). In addition, treatment reduced pain scores on a visual analogue scale by an average of 5.28 points more than placebo (p = 0.008). Scores for the timed walk did not differ significantly between treatment and placebo (p = 0.2). Scores on the Paced Auditory Serial Addition Test decreased by 8.67 points more with treatment than with placebo (p = 0.003). No serious adverse events occurred during the trial.
Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity. Future studies should examine whether different doses can result in similar beneficial effects with less cognitive impact.
In the welter of everyday life, people can stop particular response tendencies without affecting others. A key requirement for such selective suppression is that subjects know in advance which ...responses need stopping. We hypothesized that proactively setting up and implementing selective suppression relies on the basal ganglia and, specifically, regions consistent with the inhibitory indirect pathway for which there is scant functional evidence in humans. Consistent with this hypothesis, we show, first, that the degree of proactive motor suppression when preparing to stop selectively (indexed by transcranial magnetic stimulation) corresponds to striatal, pallidal, and frontal activation (indexed by functional MRI). Second, we demonstrate that greater striatal activation at the time of selective stopping correlates with greater behavioral selectivity. Third, we show that people with striatal and pallidal volume reductions (those with premanifest Huntington's disease) have both absent proactive motor suppression and impaired behavioral selectivity when stopping. Thus, stopping goals are used to proactively set up specific basal ganglia channels that may then be triggered to implement selective suppression. By linking this suppression to the striatum and pallidum, these results provide compelling functional evidence in humans of the basal ganglia's inhibitory indirect pathway.
ABSTRACT
Background
Individuals with Huntington's disease (HD) experience motoric, cognitive, and psychiatric dysfunction. These difficulties can cause maladaptive behaviors that can be very ...distressing to family and caregivers. Capturing these behaviors in clinical and research settings is crucial.
Objectives
To develop and evaluate the psychometric properties of an instrument that is brief, yet comprehensive, in assessing a broad range of behaviors in HD.
Methods
A pool of 30 items encompassing common behaviors in HD was generated. Items were scored on a 4‐point Likert scale ranging from completely disagree to completely agree, with higher scores indicating greater dysfunction. The self‐report measure was piloted on a small sample of individuals with HD. Reliability (test–retest, internal consistency) and validity (convergent, discriminant, criterion) were evaluated.
Results
The HD–Behavioral Questionnaire (HD‐BQ) demonstrated evidence for reliability with a test–retest correlation coefficient of r = 0.81 and an internal consistency of 0.96. Validity was established with evidence for good convergent, divergent, and criterion validity. A receiver operating characteristic curve showed that the HD‐BQ outperformed a similar commonly used measure in diagnostic capability of behaviors in HD.
Conclusions
The HD‐BQ, a patient self‐report measure, was created to more fully explore behavioral issues that people with HD experience in response to limitations of commonly used instruments in the field. Psychometric evidence supports that the HD‐BQ is a valid and reliable instrument for the brief, yet comprehensive, assessment of problematic behaviors in HD.
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