Characterizing Hemodynamic Compensation in Patients With Intracranial Stenosis
Condition: Stroke; Intracranial Stenosis
MeSH terms: Constriction, Pathologic
Study type: Observational

Summary: 
      The overall aim of this work is to assess the relationship between stroke risk and
      hemodynamic compensation strategies, as measured using a novel 3.0 Tesla MRI protocol, in
      patients with symptomatic intracranial (IC) steno-occlusive disease. Recent studies have
      shown high two-year ischemic stroke rates in symptomatic patients with IC arterial stenosis.
      Therapy for IC stenosis patients includes revascularization with angioplasty, IC stenting, or
      bypass, however identification of patients most likely to benefit from these more aggressive
      interventions, rather than medical management alone, has been problematic. Accurate
      measurements of hemodynamic compromise are likely required to better define stroke risk and
      guide treatment decisions. Specifically, in IC stenosis patients with compromised cerebral
      perfusion pressure (CPP), the extent of hemodynamic compromise reflects the autoregulatory
      capacity of vasculature to increase arterial cerebral blood volume (aCBV) and/or develop
      collaterals to supplement cerebral blood flow (CBF). The prevalence of CBF collateralization
      and aCBV autoregulation has been hypothesized to correlate uniquely with stroke risk, however
      the extent of this correlation has been debated. The critical barrier to stratifying stroke
      risk rests with a lack of (i) methodology for measuring multiple hemodynamic factors with
      high specificity and (ii) noninvasive approaches capable of monitoring longitudinal
      progression of impairment. The investigators have demonstrated the clinical utility of
      relatively new, noninvasive MRI approaches for assessing cerebrovascular reactivity (CVR),
      aCBV, and collateral CBF. The investigators hypothesize that stroke risk can be more
      completely evinced from collective measurements of these parameters. Therefore, the
      investigators propose to implement a novel, validated hemodynamic MRI protocol to assess
      tissue-level impairment and compensation strategies in patients with IC stenosis. Using a
      collective approach combining measurements of collateral CBF, aCBV and CVR in multiple brain
      regions, in conjunction with a statistical model incorporating the above variables as
      possible prognostic factors, the investigators will quantify the extent to which two-year
      stroke risk is associated with hemodynamic compensation mechanisms. The noninvasive and
      multi-faceted scope of this investigation is intended to expand the diagnostic stroke
      infrastructure and elucidate new hemodynamic prognostic indicators of stroke in this
      high-risk population.
    

Detailed description: 
      The overall aim of this work is to assess the relationship between stroke risk and
      hemodynamic compensation strategies, as measured using a novel 3.0 Tesla (T) MRI protocol, in
      patients with symptomatic intracranial (IC) steno-occlusive disease. Recent studies have
      shown high two-year ischemic stroke rates of approximately 20% in symptomatic IC stenosis
      patients. Aggressive therapy for IC stenosis patients includes revascularization with
      angioplasty, IC stenting, or bypass, however identification of patients most likely to
      benefit from these more aggressive interventions, rather than medical management alone, has
      been problematic. Accurate measurements of hemodynamic compromise are likely required to
      better define stroke risk and guide treatment decisions. Specifically, in IC stenosis
      patients with compromised cerebral perfusion pressure (CPP), the extent of hemodynamic
      compromise reflects the autoregulatory capacity of vasculature to increase arterial cerebral
      blood volume (aCBV) and/or develop collaterals to supplement cerebral blood flow (CBF). The
      prevalence of CBF collateralization and aCBV autoregulation has been hypothesized to
      correlate uniquely with stroke risk, however the extent of this correlation is debated.

      The critical barrier to stratifying stroke risk rests with a lack of (i) methodology for
      measuring multiple hemodynamic factors with high specificity and (ii) noninvasive approaches
      capable of monitoring longitudinal progression of impairment. The investigators have
      demonstrated the clinical utility of relatively new, noninvasive MRI approaches for assessing
      cerebrovascular reactivity (CVR), aCBV, and collateral CBF. These approaches have been
      optimized and feasibility assessed in healthy volunteers or isolated clinical studies,
      however comparatively little information is available regarding the relationship between
      these collective measures and stroke risk. Therefore, the investigators propose to complement
      established angiographic and structural imaging with more novel, validated hemodynamic
      measurements to assess tissue-level impairment and compensation strategies in patients with
      IC stenosis. Using a collective approach combining measurements of collateral CBF, aCBV and
      CVR in multiple brain regions, in conjunction with a statistical model incorporating the
      above parameters as possible prognostic factors, the investigators will quantify the extent
      to which two-year stroke risk is associated with hemodynamic compensation mechanisms in a
      population of symptomatic IC stenosis patients. The noninvasive and multi-faceted scope of
      this investigation is intended to expand the diagnostic stroke infrastructure and elucidate
      new hemodynamic prognostic indicators of stroke in this high-risk population.

      Hypothesis (1). Changes in collateral CBF with hypercarbic stimulation positively correlate
      with two-year stroke incidence in symptomatic IC stenosis patients.

      Aim (1). By separately magnetically labeling blood water in different feeding arteries (8),
      the investigators will use a tested vessel-selective arterial spin labeling (VS-ASL) approach
      and a calculated perfusion asymmetry index to noninvasively assess changes in collateral CBF
      patterns in patients with IC stenosis. IC stenosis (n=90) patients will be monitored for two
      years during which their known stroke incidence is 20%. Stroke incidence will be recorded and
      separate correlations between perfusion asymmetry and stroke risk will be assessed.

      Hypothesis (2). Regionally reduced CVR, indicative of vascular steal phenomena, and elevated
      aCBV, will positively correlate with two-year stroke incidence in symptomatic IC stenosis
      patients.

      Aim (2). CVR, as measured using the blood oxygenation level-dependent (BOLD) MRI signal
      change in response to hypercarbia, will be used to assess cerebrovascular reserve. The inflow
      vascular-space-occupancy with dynamic subtraction (iVASO-DS) approach, which we have
      developed and demonstrated in patients, will be applied to assess baseline aCBV. For the same
      patients as in Aim 1, CVR dynamics and aCBV will be statistically assessed for unique
      relationships with two-year stroke incidence.

      Hypothesis (3). Collateral CBF, autoregulatory aCBV, and CVR will correlate unequally with
      two-year stroke incidence, the extent of which can be quantified using a multi-component
      prediction model.

      Aim (3). The investigators will build a statistical prediction model, using collateral CBF,
      aCBV and CVR as prognostic factors, to quantify the extent to which trends in the above
      parameters collectively contribute to stroke risk. The high two-year stroke rate (20%) and
      large number of admitted patients with symptomatic IC stenosis, will enable this study to
      detect hypothesized group differences with high statistical power.

      This work is an extension of recent methodological work whereby a novel, collective
      compensatory hemodynamic protocol is applied to a specific clinical population to understand
      prognostic potential. Successful completion should provide new information on tissue
      hemodynamics and stroke risk in patients that can be used to guide management decisions,
      ultimately reducing stroke incidence in this high-risk population.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with intracranial stenosis who have had a stroke within the past 60 days