The Vascular Mean Transit Time: A Surrogate for the Penumbra Flow Threshold?

Carrera, Emmanuel; Jones, P. Simon; Iglesias, S.; Guadagno, Joseph V.; Warburton, Elizabeth A.; Fryer, Tim D.; Aigbirhio, Franklin I.; Baron, Jean‐Claude

doi:10.1038/jcbfm.2010.197

Cited by 31 publications

(21 citation statements)

References 43 publications

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“…Indeed, MTT was increased in patients with MS, independent of the possible coexistence of CCSVI, which suggests a possible role of regional cerebral perfusion in MS course and pathogenesis, regardless of venous malformations. In this respect, MTT is closely related to cerebral perfusion pressure (27) and to penumbra entity (28), and our findings are in good agreement with previous histopathologic evidence in MS that shows vascular occlusion (29) and/or hypoxia-like tissue injury (30). Besides focal white-matter lesions, MS brain tissue also displays abnormalities in the NAWM.…”

Section: Neuroradiology: Brain Hemodynamic Changes and Multiple Sclersupporting

confidence: 80%

Brain Hemodynamic Changes Associated with Chronic Cerebrospinal Venous Insufficiency Are Not Specific to Multiple Sclerosis and Do Not Increase Its Severity

Garaci¹,

Marziali²,

Meschini³

et al. 2012

Radiology

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Purpose:To investigate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and cerebral hemodynamic parameters and to disclose any possible involvement in the pathophysiology of multiple sclerosis (MS). Materials and Methods:The study was approved by the institutional review board, and written informed consent was obtained from all participants. The diagnosis of CCSVI was assigned by using specific color Doppler ultrasonographic criteria. Cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time were assessed with dynamic susceptibility contrast material-enhanced magnetic resonance imaging in normal-appearing white matter (NAWM) in 39 patients with MS. Of these, 25 had CCSVI and 14 did not. Twenty-six healthy control subjects were also evaluated, and of these, 14 had CCSVI and 12 did not. Twoway analysis of variance testing was used for statistical analysis, with Bonferroni correction for multiple comparisons. Correlation analysis was performed by calculating Spearman coefficients. Results:Individuals with CCSVI showed cerebral hemodynamic anomalies, such as decreased CBF and CBV, as compared with individuals without CCSVI, without any delay in mean transit time. No significant interaction between MS and CCSVI was found for any hemodynamic parameters. Furthermore, no correlations were found between CBV and CBF values in NAWM or for severity of disability in patients with MS. The MS group showed prolonged mean transit time in the periventricular NAWM, as compared with the control group, and positive correlation was found between mean transit time values and disability scales in patients with MS. Conclusion:The data support a role of CCSVI in cerebral hemodynamic changes, such as a decrease of CBV and CBF, regardless of the presence of MS. CCSVI had no effect on neurologic function and disability progression in patients with MS.q RSNA, 2012

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Section: Neuroradiology: Brain Hemodynamic Changes and Multiple Sclersupporting

confidence: 80%

Brain Hemodynamic Changes Associated with Chronic Cerebrospinal Venous Insufficiency Are Not Specific to Multiple Sclerosis and Do Not Increase Its Severity

Garaci¹,

Marziali²,

Meschini³

et al. 2012

Radiology

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“…Also, by using receiver operating characteristics analysis, improved validity of PET-derived mean transit time for predicting the penumbra threshold could be achieved [82] . More advanced analytical procedures may also help to identify more reliably the threshold between critical and non-critical hypoperfusion and to reduce variance in determined values [83] .…”

Section: Validation Of Mri Signatures On Pet Measurementsmentioning

confidence: 99%

The Ischemic Penumbra: Correlates in Imaging and Implications for Treatment of Ischemic Stroke

2011

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The concept of the ischemic penumbra was formulated 30 years ago based on experiments in animal models showing functional impairment and electrophysiological disturbances with decreasing flow to the brain below defined values (the threshold for function) and irreversible tissue damage with the blood supply further decreased (the threshold for infarction). The perfusion range between these thresholds was termed ‘penumbra’, and restitution of flow above the functional threshold was able to reverse the deficits without permanent damage. However, in further experiments, the dependency of the development of irreversible lesions on the interaction of the severity and duration of critically reduced blood flow was established – proving that the lower the flow, the shorter the time for efficient reperfusion. Therefore, infarction develops from the core of ischemia to the areas of less severe hypoperfusion. The propagation of irreversible tissue damage is characterized by a complex cascade of interconnected electrophysiological, molecular, metabolic and perfusional disturbances. Waves of depolarizations, the peri-infarct spreading depression-like depolarizations, inducing activation of ion pumps and liberation of excitatory transmitters, have dramatic consequences as drastically increased metabolic demand cannot be satisfied in regions with critically reduced blood supply. The translation of experimental concept into the basis for efficient treatment of stroke requires non-invasive methods by which regional flow and energy metabolism can be repeatedly investigated to demonstrate penumbra tissue that can benefit from therapeutic interventions. Positron emission tomography (PET) allows the quantification of regional cerebral blood flow, the regional metabolic rate for oxygen and the regional oxygen extraction fraction. From these variables, clear definitions of irreversible tissue damage and critically perfused but potentially salvageable tissue (i.e. the penumbra) can be achieved in animal models and stroke patients. Additionally, further tracers can be used for early detection of irreversible tissue damage, e.g. by the central benzodiazepine receptor ligand flumazenil. However, PET is a research tool and its complex logistics limit clinical routine applications. As a widely applicable clinical tool, perfusion/diffusion-weighted (PW/DW) MRI is used, and the ‘mismatch’ between the PW and the DW abnormalities serve as an indicator of the penumbra. However, comparative studies of PW/DW-MRI and PET have pointed to an overestimation of the core of irreversible infarction as well as of the penumbra by MRI modalities. Some of these discrepancies can be explained by unselective application of relative perfusion thresholds, which might be improved by more complex analytical procedures. Heterogeneity of the MRI signatures used for the definition of the mismatch are also responsible for disappointing results in the application of PW/DW-MRI for the selection of patients for clinical trials. As long as a validation of the mismatch selection paradigm is lacking, its use as a surrogate marker of outcome is limited.

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“…8 Dispersion may cause some components of the bolus to arrive far later. 9 Once each part of the bolus arrives, the average time that it spends in ischemic tissue is commonly 10 -20 seconds and sometimes considerably longer, 10 because autoregulatory vasodilation slows blood velocity. In comparison, CTP and MRP scans may be as short as 40 seconds.…”

mentioning

confidence: 99%