Iron, Myelin, and the Brain: Neuroimaging Meets Neurobiology.

https://pure.mpg.de/pubman/item/item_3288895_1/component/file_3288896/Lazari_2021.pdf

Can MRI measure myelin? Systematic review, qualitative assessment, and meta-analysis of studies validating microstructural imaging with myelin histology.

Several MRI measures have been proposed as in vivo biomarkers of myelin, each with applications ranging from plasticity to pathology. Despite the availability of these myelin-sensitive modalities, specificity and sensitivity have been a matter of discussion. Debate about which MRI measure is the most suitable for quantifying myelin is still ongoing. In this study, we performed a systematic review of published quantitative validation studies to clarify how different these measures are when compared to the underlying histology. We analyzed the results from 43 studies applying meta-analysis tools, controlling for study sample size and using interactive visualization (https://neurolibre.github.io/myelin-meta-analysis). We report the overall estimates and the prediction intervals for the coefficient of determination and find that MT and relaxometry-based measures exhibit the highest correlations with myelin content. We also show which measures are, and which measures are not statistically different regarding their relationship with histology.

/pdf/an-interactive-meta-analysis-of-mri-biomarkers-of-myelin-3sbmjin1q0.pdf

An interactive meta-analysis of MRI biomarkers of myelin.

Activation of innate immune cells and other compartmentalized inflammatory cells in the brains and spinal cords of people with relapsing-remitting multiple sclerosis (MS) and progressive MS has been well described histopathologically. However, conventional clinical MRI is largely insensitive to this inflammatory activity. The past two decades have seen the introduction of quantitative dynamic MRI scanning with contrast agents that are sensitive to the reduction in blood-brain barrier integrity associated with inflammation and to the trafficking of inflammatory myeloid cells. New MRI imaging sequences provide improved contrast for better detection of grey matter lesions. Quantitative lesion volume measures and magnetic resonance susceptibility imaging are sensitive to the activity of macrophages in the rims of white matter lesions. PET and magnetic resonance spectroscopy methods can also be used to detect contributions from innate immune activation in the brain and spinal cord. Some of these advanced research imaging methods for visualization of chronic inflammation are practical for relatively routine clinical applications. Observations made with the use of these techniques suggest ways of stratifying patients with MS to improve their care. The imaging methods also provide new tools to support the development of therapies for chronic inflammation in MS.

/pdf/chronic-inflammation-in-multiple-sclerosis-seeing-what-was-1umk4dr286.pdf

Chronic inflammation in multiple sclerosis - seeing what was always there.

Parkinson's disease (PD) is a complex neurodegenerative disorder with no cure in sight. Clinical challenges of the disease include the inability to make a definitive diagnosis at the early stages and difficulties in predicting the disease progression. The unmet demand to identify reliable biomarkers for early diagnosis and management of the disease course of PD has attracted a lot of attention. However, only a few reported candidate biomarkers have been tried in clinical practice at the present time. Studies on PD biomarkers have often overemphasized the discovery of novel identity, whereas efforts to further evaluate such candidates are rare. Therefore, we update the new development of biomarker discovery in PD and discuss the standard process in the evaluation and assessment of the diagnostic or prognostic value of the identified potential PD biomarkers in this review article. Recent developments in combined biomarkers and the current status of clinical trials of biomarkers as outcome measures are also discussed. We believe that the combination of different biomarkers might enhance the specificity and sensitivity over a single measure that might not be sufficient for such a multiplex disease.

Biomarkers for Parkinson's Disease: How Good Are They?

The influence of brain iron and myelin on magnetic susceptibility and effective transverse relaxation - A biochemical and histological validation study.

BACKGROUND AND PURPOSE: Susceptibility weighted imaging (SWI) plays a role in the differential diagnosis of Parkinson's disease, but lacks widespread acceptance in clinical routine. In a descriptive pilot study, we assessed hypointense microstructures of the normal substantia nigra pars compacta at ultrahigh-field strength for interpretation of the “swallow tail sign.”. METHODS: Magnetic resonance imaging at 7 Tesla was performed in five postmortem samples obtained from subjects not affected by Parkinson's disease. Susceptibility weighted images, including minimum intensity projections, were created followed by consensus assessment for microvascular confound. Histological workup in this case-control study included iron and myelin staining. Seven Tesla SWI images from the reference cohort of nine living subjects, all of which showed a positive “swallow tail sign” in their midbrains, were assessed visually. RESULTS: All specimens showed microvessels running through the dorsal pars compacta and along the caudolateral circumference of the red nucleus. Hypointense imaging patterns in the medial part of the “swallow tail” were due to susceptibility effects of iron deposits and microvessels. In eight out of nine control subjects, one or more microvessels were detected medial to the dorsolateral nigral hyperintensity or at least unilaterally in the medial part of the “swallow tail.” One microvessel crossing nigrosome 1 was found in two in-vivo cases. CONCLUSION: Both iron deposits and microvessels contribute to the hyposignal surrounding nigrosome 1 in susceptibility weighted imaging of normal aged midbrains at ultrahigh-field strength. When assessing the substantia nigra for the presence or absence of the “swallow tail sign,” intrinsic vessels may be a sporadic confounder.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jon.12576

Microvessels may Confound the "Swallow Tail Sign" in Normal Aged Midbrains: A Postmortem 7 T SW-MRI Study.

Purpose Multiplication of FLAIR and T2-weighted MRI scans results in images (called FLAIR2) with an improved contrast-to-noise ratio (CNR) for multiple sclerosis (MS) lesions but with a reduced signal-to-noise ratio (SNR). Denoising of these images may therefore further improve FLAIR2 image quality. The purpose of this work is to present a systematic investigation of FLAIR2 image denoising methods using Gaussian, Wiener and Total Generalized Variation (TGV) filtering approaches. Materials and methods T2-weighted and FLAIR data of four MS patients were used. For CNR and SNR measurements, each scan was performed up to three times. TGV, Gaussian and Wiener filtering was applied to T2, FLAIR and the FLAIR2 data. FLAIR2 images were afterwards additionally created using all combinations of input data (native, filtered T2 and filtered FLAIR). SNR and CNR measurements were performed using the subtraction method for all FLAIR2 approaches (native and filtered input data) and for twenty MS lesions. Additionally, quantitative analysis of filtering based image blurring was performed on all data sets. Results FLAIR2 images denoised with TGV showed the highest SNR and CNR, while SNR values were similar for Gaussian and Wiener filtered images. The average CNR over 20 MS lesions within the native FLAIR2 (32.99) achieved an improvement to 91.17, 82.33 and 56.07 corresponding to TGV, Wiener and Gaussian filtering. FLAIR multiplied with T2.denoised showed no improvement, while FLAIR.denoised multiplied with T2 showed an increase by a factor of two to the native, not filtered FLAIR2. Blurring was most pronounced in Gaussian filtered images and similar in TGV and Wiener filtered images. Conclusion FLAIR images filtered with Wiener or TGV multiplied with the unfiltered T2 results in FLAIR2 images with increased SNR and CNR and with minimal edge blurring.

Evelin Haimburger

Papers

The influence of brain iron and myelin on magnetic susceptibility and effective transverse relaxation - A biochemical and histological validation study.

Microvessels may Confound the "Swallow Tail Sign" in Normal Aged Midbrains: A Postmortem 7 T SW-MRI Study.

Noise reduction in FLAIR2 images using total generalized variation, Gaussian and Wiener filtering.