Cerebral Circulation Time is Prolonged and Not Correlated with EDSS in Multiple Sclerosis Patients: A Study Using Digital Subtracted Angiography

Monti, Lucia; Donati, D.; Menci, E.; Cioni, Samuele; Bellini, Matteo; Grazzini, Irene; Leonini, Sara; Galluzzi, Paolo; Severi, Sauro; Burroni, Luca; Casasco, A.; Morbidelli, Lucia; Santarnecchi, Emiliano; Piu, Pietro

doi:10.1371/journal.pone.0116681

Cited by 14 publications

(16 citation statements)

References 35 publications

(43 reference statements)

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“…= 1.27 secs) versus 2.8 seconds (s.d. = 0.51 secs) in controls [115], and in another, the median longest time in MS was 6.47 seconds (range, 3.29-29.24 seconds) versus 5.54 seconds in controls (range, 2.57-7.63 seconds; p <0.001) [116]. In particular, it is the arterial flow which is slow, with prolonged arterial bolus arrival times [94;117] even in the presence of normal venous flow [117].…”

Section: Haemodynamic Consequences Of Msmentioning

confidence: 89%

Understanding a role for hypoxia in lesion formation and location in the deep and periventricular white matter in small vessel disease and multiple sclerosis

Sosa

Smith

2017

Clinical Science

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The deep and periventricular white matter is preferentially affected in several neurological disorders, including cerebral small vessel disease (SVD) and multiple sclerosis (MS), suggesting that common pathogenic mechanisms may be involved in this injury. Here we consider the potential pathogenic role of tissue hypoxia in lesion development, arising partly from the vascular anatomy of the affected white matter. Specifically, these regions are supplied by a sparse vasculature fed by long, narrow end arteries/arterioles that are vulnerable to oxygen desaturation if perfusion is reduced (as in SVD, MS and diabetes) or if the surrounding tissue is hypoxic (as in MS, at least). The oxygen crisis is exacerbated by a local preponderance of veins, as these can become highly desaturated 'sinks' for oxygen that deplete it from surrounding tissues. Additional haemodynamic deficiencies, including sluggish flow and impaired vasomotor reactivity and vessel compliance, further exacerbate oxygen insufficiency. The cells most vulnerable to hypoxic damage, including oligodendrocytes, die first, resulting in demyelination. Indeed, in preclinical models, demyelination is prevented if adequate oxygenation is maintained by raising inspired oxygen concentrations. In agreement with this interpretation, there is a predilection of lesions for the anterior and occipital horns of the lateral ventricles, namely regions located at arterial watersheds, or border zones, known to be especially susceptible to hypoperfusion and hypoxia. Finally, mitochondrial dysfunction due to genetic causes, as occurs in leucodystrophies or due to free radical damage, as occurs in MS, will compound any energy insufficiency resulting from hypoxia. Viewing lesion formation from the standpoint of tissue oxygenation not only reveals that lesion distribution is partly predictable, but may also inform new therapeutic strategies.

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Section: Haemodynamic Consequences Of Msmentioning

confidence: 89%

Understanding a role for hypoxia in lesion formation and location in the deep and periventricular white matter in small vessel disease and multiple sclerosis

Sosa

Smith

2017

Clinical Science

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“…Intravascular contrast medium injection was done in the internal carotid artery. Images were analyzed to determine CCT, as previously described 25. Cerebral circulation time is the frame time between the beginning (arterial inflow) and the end (venous outflow) of the whole cerebral blood flow.…”

Section: Methodsmentioning

confidence: 99%

“…Lesion loads (LL) were analyzed in a subsample of 25 patients with MS, as previously described 25. The subsample was defined on the basis of the same MRI parameters, such as intensity fields, technical approach, and image quality.…”

Section: Methodsmentioning

confidence: 99%

Influence of Circulating Endothelin-1 and Asymmetric Dimethylarginine on Whole Brain Circulation Time in Multiple Sclerosis

et al. 2017

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Blood-brain barrier (BBB) breakdown, inflammatory and immune cell activation, and chronic cerebral hypoperfusion are features of multiple sclerosis (MS). The aim is to determine the influence of endothelin-1 (ET1) and asymmetric dimethylarginine (ADMA) on cerebral circulation time (CCT) in patients with MS. In all, 64 patients with MS (39 relapsing-remitting [RR]-MS; 25 secondary progressive [SP]-MS subtype) and 37 controls (C) were studied. Cerebral circulation time was obtained by angiography. Plasmatic ET1 and ADMA were measured by enzyme-linked immunosorbent assay. Lesion load (LL) and brain volume (BV) were obtained by magnetic resonance imaging. Cerebral circulation time was correlated to ET1, ADMA, LL, BV, disease duration (DD), and Expanded Disability Status Scale (EDSS). In MS, both ET1 and ADMA were significantly higher than C (P < .0001); CCT was approximately 2 times lower than C (P < .0001) and significantly slower in SP than in RR-MS (P = .0215). Cerebral circulation time significantly correlated with ET1 in SP-MS (r = 0.38), whereas in RR-MS CCT significantly correlated with DD (r = 0.75). The LL, BV, and EDSS did not correlate with CCT. Endothelin-1 significantly influences CCT delay in SP-MS. Diversely, CCT in RR-MS is independent of ET1 and correlates significantly with DD. We conclude that in RR-MS, DD responds to neurovascular damage accumulation. It is supposed that high ET1 and ADMA levels stem from a protective response to early insults, aimed at opposing nitric oxide overproduction, whereas persistent pathological ET1 and ADMA levels translate into detrimental long-term effects, due to increased brain micro-vessel resistance.

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“…Similar, but smaller delays (4.9–6.4 s) were found in other ultrasound studies (Schreiber et al, 2005). Direct evidence can also be found in digital subtraction angiography (DSA), where an x-ray contrast bolus was injected directly into the ICA and followed as it passed through the brain (Monti et al, 2015; Jann et al, 2016).…”

Section: Characteristics Of Low Frequency Oscillationsmentioning

confidence: 99%

Low Frequency Systemic Hemodynamic “Noise” in Resting State BOLD fMRI: Characteristics, Causes, Implications, Mitigation Strategies, and Applications

2019

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Advances in functional magnetic resonance imaging (fMRI) acquisition have improved signal to noise to the point where the physiology of the subject is the dominant noise source in resting state fMRI data (rsfMRI). Among these systemic, non-neuronal physiological signals, respiration and to some degree cardiac fluctuations can be removed through modeling, or in the case of newer, faster acquisitions such as simultaneous multislice acquisition, simple spectral filtering. However, significant low frequency physiological oscillation (∼0.01–0.15 Hz) remains in the signal. This is problematic, as it is the precise frequency band occupied by the neuronally modulated hemodynamic responses used to study brain connectivity, precluding its removal by spectral filtering. The source of this signal, and its method of production and propagation in the body, have not been conclusively determined. Here, we summarize the defining characteristics of the systemic low frequency noise signal, and review some current theories about the signal source and the evidence supporting them. The strength and distribution of the systemic LFO signal make characterizing and removing it essential for accurate quantification, especially for resting state connectivity, when no stimulation can be compared with the signal. Widespread correlated non-neuronal signals obscure and distort the more localized patterns of neuronal correlations between interacting brain regions; they may even cause apparent connectivity between regions with no neuronal interaction. Here, we discuss a simple method we have developed to parse the global, moving, blood-borne signal from the stationary, neuronal connectivity signals, substantially reducing the negative correlations that result from global signal regression. Finally, we will discuss some of the uses to which the moving systemic low frequency oscillation can be put if we consider it a “signal” carrying information, rather than simply “noise” complicating the interpretation of resting state connectivity. Properly utilizing this signal may offer insights into subtle hemodynamic alterations that can be used as early indicators of circulatory dysfunction in a number of neuropsychiatric conditions, such as prodromal stroke, moyamoya, and Alzheimer’s disease.

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Cerebral Circulation Time is Prolonged and Not Correlated with EDSS in Multiple Sclerosis Patients: A Study Using Digital Subtracted Angiography

Cited by 14 publications

References 35 publications

Understanding a role for hypoxia in lesion formation and location in the deep and periventricular white matter in small vessel disease and multiple sclerosis

Understanding a role for hypoxia in lesion formation and location in the deep and periventricular white matter in small vessel disease and multiple sclerosis

Influence of Circulating Endothelin-1 and Asymmetric Dimethylarginine on Whole Brain Circulation Time in Multiple Sclerosis

Low Frequency Systemic Hemodynamic “Noise” in Resting State BOLD fMRI: Characteristics, Causes, Implications, Mitigation Strategies, and Applications

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