C-Arm Flat Detector CT Parenchymal Blood Volume Thresholds for Identification of Infarcted Parenchyma in the Neurointerventional Suite

Discussion

This study reports optimal absolute and normalized C-arm CT PBV threshold values for demarcating irreversibly infarcted brain parenchyma in the neurointerventional suite.

In determining the PBV threshold for infarcted brain parenchyma, areas of restricted diffusion identified on the review of DWI and ADC maps were used as a marker for irreversibly infarcted tissue. Although DWI abnormality is not perfectly specific for infarct core, it is highly accurate and is an accepted standard for both clinical care and research analysis.^13⇓–15 In our analysis, we used 3D VOIs, defined semiautomatically for the DWI abnormality (infarcted parenchyma), which, along with mirrored contralateral homologous tissue VOIs, were transposed onto the coregistered C-arm CT PBV maps before performing the ROC curve analysis. This objective approach toward image analysis reduces any bias that may be introduced due to subjective differences in image display, such as color look-up tables for PBV maps, window settings, and pixel conspicuity, which can be sources of error for manual segmentation.⁷

That any perfusion study represents a “snapshot in time” and the cerebral hemodynamics and thresholds for ischemic damage may vary with time are issues well-recognized from CTP imaging of acute brain ischemia. For acute stroke imaging, this limitation may be addressed through stratifying data by duration post-ictus.⁷ However, unlike acute ischemic stroke, the complex pathophysiology of cerebral vasospasm and resulting hemodynamic alterations make it difficult to define a specific time-of-onset for DCI secondary to vasospasm. Moreover, the limited number of patients in our study precluded any such analysis, which could theoretically be performed by using an arbitrary time point such as the development of neurologic deficits in patients post-SAH.

An important factor that may introduce variability in C-arm CT PBV measurements and consequently shift the optimal PBV thresholds for infarction is how well the steady-state assumption is met. For calculation of C-arm CT PBV, the intravenously administered iodinated contrast material is assumed to have reached a steady-state concentration in the cerebral vasculature (contrast concentration in arteries = contrast concentration in tissues = contrast concentration in veins), maintained for the duration of the scan.¹ If this assumption is fully met, the C-arm CT PBV would be equivalent to the CBV derived from dynamic perfusion imaging modalities. However, an ideal steady-state may not be achieved in practice for the clinical scans, and the contrast profile in the cerebral vasculature may show intersubject differences due to various factors such as recirculation of contrast, hemodynamic perturbation effect, and slow bolus transit in the setting of low cardiac output and multifocal vasospasm.¹⁶

Preferential contrast wash-in or washout during the acquisition of fill run data for the C-arm CT PBV study (8 seconds) may result in variable blood flow weighting to the calculated PBV. In a separate analysis for the same cohort (subject of another publication), we found that for clinical examinations, the C-arm CT PBV has ≈60% CBF and 40% CBV weighting, with similar supporting observations for multidetector CT.^5,17 Thus, differences in contrast dynamics can result in differences in blood flow and blood volume weighting to PBV, which can translate into differences in final PBV measurements. Assuming identical contrast dynamics or an ideal steady-state in all patients despite the differences in their hemodynamic physiology may overlook the blood flow weighting to C-arm CT PBV, particularly in cases in which the time-attenuation curves depart from the steady-state, thus potentially resulting in overestimation (or underestimation) of irreversibly infarcted parenchyma when using a specific threshold. This limitation can be overcome by a simple ROI-based time-attenuation-curve analysis of the raw C-arm CT projection data for the clinical PBV scans, which can provide an estimate of how adequately the steady-state contrast concentration was achieved during a particular study.

Our results indicate that the measured PBV values in the peri-infarct ischemic tissue may or may not show reduction, depending on the severity of the ischemic insult. We found that in moderate-to-severely ischemic peri-infarct tissue (relative MR CBF, <75%), the PBV measurements showed statistically significant reduction compared with the contralateral uninvolved homologous tissue. However, PBV values in the mild-to-moderately ischemic peri-infarct parenchyma (relative MR CBF, 75%–95%) were not significantly reduced relative to the contralateral uninvolved homologous tissue. The peri-infarct ischemic zone we identified for analysis is conceptually similar to the penumbra region seen in the setting of acute ischemic stroke. These findings are interesting and can be explained by the combined blood volume and blood flow weighting to C-arm CT PBV. CT perfusion reveals that in the setting of acute ischemic stroke, the infarcted tissue shows a matched decrease in CBV and CBF.^18,19 However, the ischemic tissue surrounding the infarct core has only reduced CBF, while the CBV may be maintained or elevated secondary to autoregulatory hemodynamics whereby precapillary vessels dilate in response to decreased cerebral perfusion pressure.¹⁹ In the setting of severe or prolonged ischemia, the autoregulatory mechanisms fail, leading to eventual reduction in CBV. The degree to which the CBF is reduced and whether the CBV is elevated, maintained, or reduced are thus functions of the severity of the ischemic insult. In a separate analysis for the same cohort, we found that with combined blood volume and blood flow weighting (subject of another publication), C-arm CT PBV behaves as a composite parameter. Thus, in the irreversibly infarcted tissue, due to an underlying matched decrease in CBV and CBF, we see a definitive reduction in PBV (Fig 3A). In the peri-infarct ischemic region of reduced CBF, PBV would be maintained when the ischemic insult is less severe and the autoregulatory mechanisms are intact and effective in increasing the regional CBV (Fig 3C). On the contrary, PBV measurements would be reduced if the ischemia is prolonged or worsens in severity with consequent impaired autoregulation, ineffective in increasing or maintaining the CBV (Fig 3B). Therefore, C-arm CT PBV measurements would reliably detect moderate-to-severe ischemia but can potentially underestimate mild-to-moderate ischemia.

We recognize that C-arm CT PBV imaging cannot replace DWI, which is highly accurate in the demarcation of irreversibly infarcted brain parenchyma. However, its availability in the neurointerventional suite is a unique advantage with implications for management of acute cerebrovascular ischemia. Struffert et al⁴ proposed that PBV maps may potentially be used to guide revascularization procedures through their ability to monitor the brain viability. In this regard, a single C-arm CT study can provide both the anatomic and physiologic data for patients with acute stroke in the interventional suite without the need to transfer patients to CT or MR imaging facilities. For example, the C-arm CT soft-tissue images can reliably exclude intracranial hemorrhage, the angiographic reconstructions can help evaluate proximal vessel occlusion, and the PBV maps provide patient-specific physiologic data that can potentially be used, instead of the more generalized and nonspecific time criteria, in selecting appropriate patients for acute stroke interventions, particularly when a significant delay exists between initial imaging and patient arrival in the angiography suite.^4,20 Similarly, in the patients with aneurysmal SAH who develop delayed clinical deterioration, the PBV maps can be used to determine the hemodynamic significance of vessel narrowing detected on catheter angiography and to identify any ongoing ischemia or established infarcts, thus guiding the angioplasty procedures. For these applications, extended craniocaudal coverage allowing whole-brain PBV measurements would be particularly beneficial—for example, the changes related to vasospasm may be multifocal or global in nature and the acute ischemic stroke may be in a distribution located outside the traditional supratentorial coverage of CTP and may thus be better evaluated with extended craniocaudal coverage of C-arm CT PBV.

For CTP and PWI, thresholds of various perfusion parameters have been studied to demarcate the irreversibly infarcted parenchyma, and it is widely recognized that the generalizability of any specific threshold may be limited secondary to marked differences across different algorithms and postprocessing software.^17,21 For C-arm CT PBV measurement, currently only 1 commercially available application (syngo Neuro PBV IR; Siemens) exists. It is conceivable that in the future other similar postprocessing platforms will become available, in which case the validation of thresholds reported in this study across different platforms would be imperative.

The mean interval between the C-arm CT and MR imaging examinations in this study was 124 minutes, a duration during which the hemodynamics of the parenchymal areas included in the analysis may have altered; this change could result in an over- or underestimation of the reported thresholds. The observations in this study should therefore be interpreted allowing for this limitation. Additionally, optimal PBV thresholds reported in this study were assessed for whole-brain tissue VOIs. However, differences between the gray and white matter exist regarding cellular composition, metabolism, the normal perfusion parameter values, and their neurochemical responses to ischemia.^22⇓–24 Tissue-specific infarction thresholds may thus be more informative in predicting the tissue outcomes in the setting of cerebrovascular ischemia.²⁵ In our cohort, the limited number of patients and DWI lesions precluded such tissue-specific analysis to explore the differential variability of gray and white matter to ischemia. Future studies, including a larger number of patients with cerebral ischemia, may help in addressing this issue.