Inhomogeneous Magnetization Transfer (ihMT) is a development from the MT MRI technique. IhMT can be considered as a dipolar order relaxation time (T1D) weighted imaging modality whose signal has ...shown an enhanced selectivity for myelin-rich structures. However, a formal validation of the ihMT sensitivity relative to a gold standard myelin density measurement has not yet been reported. To address this need, we compared ihMT MRI with green fluorescence protein (GFP) microscopy, in a study performed on genetically-modified plp-GFP mice, considered as a reference technique for myelin-content assessment. Various ihMT protocols consisting of variable T1D-filtering and radiofrequency power temporal distributions, were used for comparison with fluorescence microscopy. Strong and significant linear relationships (r2 (0.87–0.96), p < 0.0001) were found between GFP and ihMT ratio signals across brain regions for all tested protocol variants. Conventional MT ratios showed weaker correlations (r2 (0.24–0.78), p ≤ 0.02) and a much larger signal fraction unrelated to myelin, hence corresponding to a much lower specificity for myelin. T1D-filtering reduced the ihMT signal fraction not attributed to myelin by almost twofold relative to zero filtering suggesting that at least half of the unrelated signal has a substantially shorter T1D than myelin. Overall, these results strongly support the sensitivity of ihMT to myelin content.
Validation of ihMT as a myelin sensitive technique by comparison of ihMTR values derived from various RF irradiation preparations with GFP fluorescence intensity, measured in different brain structures. Display omitted
•Inhomogeneous magnetization transfer (ihMT) was validated as a myelin sensitive imaging technique against fluorescence microscopy.•IhMT signal was strongly and significantly correlated with myelin-related plp-GFP (proteolipid - Green Fluorescence Protein) signal.•Short dipolar relaxation time (T1D) filtering is an efficient way to reduce non-myelin contribution in ihMT signal.•MT signal was more weakly correlated with plp-GFP signal and had a much larger non-myelin contribution.•IhMT contrast can be modulated with pulse timing, leading to signals with variable sensitivity and specificity for myelin.
IntroductionMindfulness meditation is likely to promote better management of stress, pain and negative emotions. We propose to address the benefit of meditation in an open setting associating people ...with cancer (target population), medical staff and witnesses (neither patient nor medical staff). This study aims (1) to evaluate the effects of meditation on wellness improvement and (2) to identify criteria and modalities for a subsequent randomised study.Methods and analysisWe propose a longitudinal pilot study consisting of a non-randomised experimental preintervention/postintervention survey. The intervention consists in delivering a meditation programme (12 weekly meditation sessions of 1.5 hours each), specifically adapted to our target population and addressing our research hypothesis in an open setting involving people with cancer, medical staff and witnesses (equally distributed in two groups of 15 participants). The main objective is to evaluate participants’ adherence to the programme. The effects of meditation will be evaluated on stress, quality of life, feeling of personal effectiveness, on the development of mindfulness and empathy, and on satisfaction and perception of a change in quality of life. We will also measure the putative added value of ‘meditating together’. This study is expected to allow validating the evaluation tools and refining the modalities of the workshops. We expect to demonstrate the evolution that this meditation-based intervention induces in the participants. We aim to promote bridge-building, between patients, medical staff but also others. In this way, one’s own suffering may be understood in the light of others’ suffering, thereby promoting the sense of otherness and giving insights into ‘living better with’. This exploratory study will investigate the relevance of this hypothesis, which could then be explored by a randomised study.Ethics and disseminationThe protocol was approved by the local ethics committee (Comité de Protection des Personnes Est II). Trial findings will be published in peer-reviewed journals.Trial registration numberNCT04410185.
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•Inclusion of a dipolar reservoir in quantitative MT allows modeling of the ihMT signal.•Differential effects of single vs. dual saturation on dipolar order explain ihMT.•The dipolar ...model implies ihMT is highly sensitive to the dipolar relaxation time T1D.•The results support ihMT's ability to detect specific motion restricted molecules.•The model may guide further research, sequence optimization, and clinical application.
Comparison of off-resonance saturation with single and dual frequency irradiation indicates a contribution of inhomogeneously broadened lines to magnetization transfer in tissues. This inhomogeneous magnetization transfer (ihMT) phenomenon can be exploited to produce images that highlight tissues containing myelin, in vivo. Here, a model for ihMT is described that includes dipolar order effects from magnetization associated with motion-restricted macromolecules. In this model, equal irradiation at positive and negative frequency offsets eliminates dipolar order and achieves greater saturation than irradiation at a single offset frequency using the same power. Fitting of mouse and human volunteer brain data at different irradiation powers and offset frequencies was performed to assess the relevance of the model and approximate tissue parameters. A key parameter in determining ihMT signal was found to be the relaxation time T1D associated with the dipolar order reservoir and the fraction f of the semi-solid, bound magnetization that possessed a nonzero T1D. Indeed, better fits of myelinated tissue were achieved when assuming f≠1. From such fits, estimated T1Ds of mice in the white matter, (34±14)ms, were much longer than in muscle, T1D=(1±1)ms and the average f from white matter volunteer data was 2.2 times greater than that in grey matter. The combination of f and longer T1Ds was primarily responsible for the much higher ihMT in myelinated tissues, and provided explanation for the species variation. This dipolar order ihMT model should help guide future research, pulse sequence optimization, and clinical applications.
Inhomogeneous magnetization transfer is a new endogenous MR imaging contrast mechanism that has demonstrated high specificity for myelin. Here, we tested the hypothesis that inhomogeneous ...magnetization transfer is sensitive to pathology in a population of patients with relapsing-remitting MS in a way that both differs from and complements conventional magnetization transfer.
Twenty-five patients with relapsing-remitting MS and 20 healthy volunteers were enrolled in a prospective MR imaging research study, whose protocol included anatomic imaging, standard magnetization transfer, and inhomogeneous magnetization transfer imaging. Magnetization transfer and inhomogeneous magnetization transfer ratios measured in normal-appearing brain tissue and in MS lesions of patients were compared with values measured in control subjects. The potential association of inhomogeneous magnetization transfer ratio variations with the clinical scores (Expanded Disability Status Scale) of patients was further evaluated.
The magnetization transfer ratio and inhomogeneous magnetization transfer ratio measured in the thalami and frontal, occipital, and temporal WM of patients with MS were lower compared with those of controls (
< .05). The mean inhomogeneous magnetization transfer ratio measured in lesions was lower than that in normal-appearing WM (
< .05). Significant (
< .05) negative correlations were found between the clinical scores and inhomogeneous magnetization transfer ratio measured in normal-appearing WM structures. Weaker nonsignificant correlation trends were found for the magnetization transfer ratio.
The sensitivity of the inhomogeneous magnetization transfer technique for MS was highlighted by the reduction in the inhomogeneous magnetization transfer ratio in MS lesions and in normal-appearing WM of patients compared with controls. Stronger correlations with the Expanded Disability Status Scale score were obtained with the inhomogeneous magnetization transfer ratio compared with the standard magnetization transfer ratio, which may be explained by the higher specificity of inhomogeneous magnetization transfer for myelin.
Hormone therapy provides an excellent survival rate after cancer but has many side effects, including joint pain in one out of two women. This leads about 13 % of women to stop their treatment within ...the first 6 months, impacting on its effectiveness, survival and the risk of recurrence. In order to better manage pain and quality of life, physical activity is highly recommended. In this context, the present review proposes a state of the art on the effects of adapted physical activity, based on the works referenced in PubMed. These studies show that physical activity has proved its worth in the primary prevention of cancer and is being evaluated in secondary prevention, particularly in the reduction of adverse effects. Overall, there is a reduction in joint pain, an improvement in quality of life and fatigue. Physical activity also plays a role in tertiary prevention. Paradoxically, oncologists and educators often note a reduction in the practice of physical activity due to fear of the onset of pain. It seems necessary to reinforce communication with patients and health professionals and to recommend the practice of physical activity in an appropriate setting.
Accurate quantification of WM lesion load is essential for the care of patients with multiple sclerosis. We tested whether the combination of accelerated 3D-FLAIR and denoising using deep ...learning-based reconstruction could provide a relevant strategy while shortening the imaging examination.
Twenty-eight patients with multiple sclerosis were prospectively examined using 4 implementations of 3D-FLAIR with decreasing scan times (4 minutes 54 seconds, 2 minutes 35 seconds, 1 minute 40 seconds, and 1 minute 15 seconds). Each FLAIR sequence was reconstructed without and with denoising using deep learning-based reconstruction, resulting in 8 FLAIR sequences per patient. Image quality was assessed with the Likert scale, apparent SNR, and contrast-to-noise ratio. Manual and automatic lesion segmentations, performed randomly and blindly, were quantitatively evaluated against ground truth using the absolute volume difference, true-positive rate, positive predictive value, Dice similarity coefficient, Hausdorff distance, and F1 score based on the lesion count. The Wilcoxon signed-rank test and 2-way ANOVA were performed.
Both image-quality evaluation and the various metrics showed deterioration when the FLAIR scan time was accelerated. However, denoising using deep learning-based reconstruction significantly improved subjective image quality and quantitative performance metrics, particularly for manual segmentation. Overall, denoising using deep learning-based reconstruction helped to recover contours closer to those from the criterion standard and to capture individual lesions otherwise overlooked. The Dice similarity coefficient was equivalent between the 2-minutes-35-seconds-long FLAIR with denoising using deep learning-based reconstruction and the 4-minutes-54-seconds-long reference FLAIR sequence.
Denoising using deep learning-based reconstruction helps to recognize multiple sclerosis lesions buried in the noise of accelerated FLAIR acquisitions, a possibly useful strategy to efficiently shorten the scan time in clinical practice.
PREVOST V. & GRACH M.‐C. (2012) European Journal of Cancer Care21, 581–590
Nutritional support and quality of life in cancer patients undergoing palliative care
In palliative care, the nutrition ...provided has to be tailored to the patient's needs, enhancing patient comfort and quality of life (QoL). We conducted a literature search to review methods of measuring QoL, and modalities of nutritional intervention and their influence on QoL of cancer patients in palliative care. Original papers published in English were selected from PubMed database by using the search terms, palliative medicine, cancer, nutrition and quality of life. Specific tools that are particularly recommended to assess QoL in a palliative care setting are reviewed. The main goal in palliative care is to maintain oral nutrition by providing nutritional counselling. Enteral nutritional support showed inconsistent effects on survival and QoL. An evidence‐base for parenteral nutrition is still lacking. Ethical considerations concerning provision of food and hydration in end‐of‐life care are discussed. Nutritional status should be assessed early and regularly during treatment using appropriate tools. In the particularly acute context of palliative care, optimal patient management requires adequate education and counselling to patients and families. Meaningful interactions between the patient, caregivers and medical team would also increase the chance of resolving nutrition‐related issues and help to fulfil each patient's specific nutritional needs and thus improve the QoL.
Purpose
In diffusion MRI (dMRI), it remains unclear to know how much increase of
b
-value is conveying additional biological meaning. We tested the correlations between cortical microarchitecture and ...diffusion metrics computed from standard (1000 s/mm
2
), high (3000 s/mm
2
), to very high (5000 s/mm
2
)
b
-value dMRI.
Methods
Healthy volunteers were scanned with a dMRI pulse sequence that was first optimized together with a T1-WI and T2-WI. Averaged cortical surface map of estimated myelin (T1-WI/T2-WI) was compared with surface maps of mean diffusivity (MD) computed from each
b
-value (MD
1000
, MD
3000
, and MD
5000
) and to surface map of mean kurtosis (MK computed from the 0-, 1000-, to 3000-s/mm
2
shells) in 360 cortical parcels using Spearman correlations, multiple linear regressions, and Akaike information criteria (AIC).
Results
Surface map from MD
1000
showed variations not related to myelin but the MD
3000
and MD
5000
maps inversely mirrored estimated myelin map; lower MD values being observed in more myelinated cortical areas. MK mirrored myelinated cortical areas. Quantitatively, Spearman correlations between myelin and MD became more and more negative as long as
b
-values increased while the correlation was positive between myelin and MK. Multiple regression models confirmed negative associations between myelin and MD that were significantly better from MD
1000
to MD
3000
and MD
5000
(
R
2
= 0.33,
p
< 0.001;
R
2
= 0.43,
p
< 0.001; and
R
2
= 0.50,
p
< 0.001) and positive association between myelin and MK (
R
2
= 0.53,
p
< 0.001). Comparisons of the 3 statistical models showed the best performances with MK and MD
5000
(AIC
MK
< AIC
MD5000
< AIC
MD3000
< AIC
MD1000
).
Conclusion
Higher
b
-values are more closely related to subtle cellular variations of the cortical microarchitecture.
Display omitted
•Reduced RF duty-cycle strongly affects some MT phenomena.•Brain tissue ihMT increased up to 3 fold going from a 50% to 5% duty-cycle.•Muscle ihMT increased even more, reducing ...contrast relative to the brain.•Methods to calculate an MT/ihMT model with reduced duty-cycle were implemented.•Experimental increases in ihMT at low duty-cycles were consistent with theory.
Intense off-resonant RF irradiation can lead to saturation of the macromolecular pool magnetization and enhance bound pool dipolar order responsible for the inhomogeneous magnetization transfer (ihMT) effect, but the intensity of RF power in human imaging studies is limited by safety constraints on RF heating. High RF intensities can still be achieved if applied in short pulses with low duty-cycle. Here we investigate the benefits of low duty-cycle irradiation for MT and ihMT studies with both theoretical and experimental methods.
Solutions for pulsed irradiation of a two-pool model including dipolar order effects were implemented. Experiments were conducted at 3 T in the brain and through the calf of healthy human subjects. 2D echo planar images were acquired following a preparation of RF irradiation with a 2 s train of 5 ms pulses repeated from between 10 to 100 ms for duty-cycles (DCs) of 50% to 5%, and at varying offset frequencies, and time averaged RF powers. MT and ihMT data were measured in regions of interest within gray matter, white matter and muscle, and fit to the model.
RF irradiation effects on signal intensity were reduced at 5% relative to 50% DCs. This reduced RF effect was much larger for single than dual frequency irradiation. 5% DC irradiation reduced single and dual frequency MT ratios but increased ihMT ratios up to 3 fold in brain tissues. Muscle ihMT increased by an even larger factor, depending on the frequency and applied power. The model predicted these changes with duty-cycle. The model fit the data well and constrained model parameters.
Low duty-cycle pulsed irradiation reduces MT effects and markedly increases dipolar order effects. This approach is an attractive method to enhance ihMT signal-to-noise ratio and demonstrates a measurable ihMT effect in muscle tissue at 3 T under acceptable specific absorption rates. The effects of duty-cycle changes demonstrated in a separate MT/ihMT preparation provide a route for new applications in magnetization-prepared MRI sequences.
A pulsed inhomogeneous magnetization transfer (ihMT)‐prepared fast imaging sequence was implemented at 11.75 T for preclinical studies on mouse central nervous system. A strategy based on filtering ...the ihMT signal originating from short dipolar relaxation time (T1D) components is proposed. It involves increasing the repetition time of consecutive radiofrequency (RF) pulses of the dual saturation and allows improved signal specificity for long T1D myelinated structures. Furthermore, frequency offset, power and timing saturation parameters were adjusted to optimize the ihMT sensitivity. The optimization of the ihMT sensitivity, whilst preserving the strong specificity for the long T1D component of myelinated tissues, allowed measurements of ihMT ratios on the order of 4–5% in white matter (WM), 2.5% in gray matter (GM) and 1–1.3% in muscle. This led to high relative ihMT contrasts between myelinated tissues and others (~3–4 between WM and muscle, and ≥2 between GM and muscle). Conversely, higher ihMT ratios (~6–7% in WM) could be obtained using minimal T1D filtering achieved with short saturation pulse repetition time or cosine‐modulated pulses for the dual‐frequency saturation. This study represents a first stage in the process of validating ihMT as a myelin biomarker by providing optimized ihMT preclinical sequences, directly transposable and applicable to other preclinical magnetic fields and scanners. Finally, ihMT ratios measured in various central nervous system areas are provided for future reference.
A strategy based on filtering of the signal of short T1D components was used to optimize the inhomogeneous magnetization transfer (ihMT) contrast for long T1D myelinated structures in mouse. Typical ihMT ratio (ihMTR) values on the order of 4‐5% in white matter (WM), 2.5% in gray matter (GM) and 1‐1.3% in muscle were obtained, thus leading to high positive relative ihMTR contrasts between myelinated tissues and other tissues. Of particular importance, the relative ihMTR contrast between WM and GM (˜2) appeared to be relatively independent of the saturation parameters.
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