Middle Cerebral Artery

The trial was performed at 38 centers in the United States. Neurointerventionalists were preapproved to participate on the basis of training and experience. (For approval requirements, see the Supplementary Appendix, available with the full text of this article at NEJM.org.) Enrolled patients or their surrogates provided written informed consent. Patients were enrolled if they met clinical and imaging eligibility requirements and could undergo initiation of endovascular therapy between 6 and 16 hours after the time that they had last been known to be well, including if they had awakened from sleep with symptoms of a stroke. Perfusion imaging had to be performed at the trial-site hospital in which endovascular therapy was planned.
Patients were eligible if they had an initial infarct volume (ischemic core) of less than 70 ml, a ratio of volume of ischemic tissue to initial infarct volume of 1.8 or more, and an absolute volume of potentially reversible ischemia (penumbra) of 15 ml or more. Estimates of the volume of the ischemic core and penumbral regions from CT perfusion or MRI diffusion and perfusion scans were calculated with the use of RAPID software (iSchemaView), an automated image postprocessing system. The size of the penumbra was estimated from the volume of tissue for which there was delayed arrival of an injected tracer agent (time to maximum of the residue function [Tmax]) exceeding 6 seconds.^{8 (link)} (An example is given in Fig. 1.) Patients were required to have an occlusion of the cervical or intracranial internal carotid artery or the proximal middle cerebral artery on CT angiography (CTA) or magnetic resonance angiography (MRA). Detailed inclusion and exclusion criteria for the trial are provided in the Supplementary Appendix.

Patients were attached to either an INVOS (Somenetics, Inc., Troy, MI) or Foresight (CAS Medical Systems, Branford, CT) NIRS monitor, depending on availability. Electrodes for monitoring NIRS were placed on the right and left forehead using the respective manufacturer’s recommendations and after first cleaning the skin with an alcohol swab. Transcranial Doppler monitoring (Doppler Box, DWL, Compumedics, USA, Charlotte, NC) of the middle cerebral arteries was with two 2.5-MHz transducers fitted on a headband. The depth of insonation varied between 35 and 52 mm until representative spectral artery flow was identified.
Analog arterial pressure data from the operating room hemodynamic monitor, TCD, and NIRS signals were sampled with an analog-to-digital converter at 60 Hz and then processed with ICM+ software version 6.1 (University of Cambridge, Cambridge, UK). These signals were time-integrated as non-overlapping 10-second mean values, which is equivalent to applying a moving average filter with a 10-second time window and re-sampling at 0.1 Hz. This operation was used to eliminate high-frequency noise from the respiratory and pulse frequencies, while allowing detection of oscillations and transients that occur below 0.05 Hz. Doppler, oximetry, and arterial blood pressure waveforms were further high pass filtered with a DC cutoff set at 0.003 Hz. This step removed slow drifts associated with hemodilution at the onset of bypass, blood transfusions, cooling, and rewarming. A continuous, moving Pearson’s correlation coefficient was calculated between the MAP and TCD blood flow velocities and between MAP and NIRS data, rendering the variables Mx (mean velocity index) and COx (cerebral oximetry index), respectively. Of note, MAP is used in this calculation and not cerebral perfusion pressure since intracranial pressure data are not available and since central venous pressure is often negative as a result of suction assisted venous drainage to the CPB reservoir. Consecutive, paired, 10-second averaged values from 300 seconds duration were used for each calculation, incorporating 30 data points for each index. Intact CBF autoregulation is indicated by an Mx value of approximately zero (CBF and MAP are not correlated), and CBF dysautoregulation is indicated by an Mx value approaching +1 (CBF and MAP correlated). Similar findings occur experimentally with COx.^{13 (link)}

Phantom, volunteer, and patient studies were performed to assess the efficacy of corrections and image quality. Data were acquired covering a 22×22×22 cm³ field of view with 0.6 mm isotropic resolution (nominal). A 75% fractional echo was used with a 62.50 kHz readout and 125 kHz receiver bandwidth. The velocity encoding (VENC) was set to 60 cm/s, resulting in a TR of 11.6 ms and TE’s of 3.5 and 6.1ms. A 15° flip angle was used in all cases, chosen based on empirical observations to minimize signal saturation. A total of 14,000 projections (28000 TRs) were collected for a total scan time of 5:24 minutes, representing an under sampling factor of 11 with respect to Nyquist. Trajectory calibrations were performed using 16 averages per direction with a 15° flip angle and a 40 ms TR; adding an additional 23 s to the exams. For all experiments an 8 channel phased array head coil was used for acquisition (HD Brain Coil, GE Healthcare, Milwaukee, WI). All reconstructions were performed using an optimized gridding operation (20 (link)) with conjugate phase reconstruction performed using least squares interpolations of 7 evenly spaced frequencies (21 (link)). Off-resonance maps were created using low-resolution phase images between echoes, with phase aliasing removed using a simple region growing algorithm. From the reconstructed velocity and magnitude images, an angiographic image was created using:
$$\mathit{CD}=\{\begin{array}{cc}\hfill M\cdot \sin (\frac{\pi }{2}\cdot \mid \overrightarrow{V}\mid ∕V_A)\hfill & \hfill \mid \overrightarrow{V}\mid <V_A\hfill \\ \hfill M\hfill & \hfill \text{otherwise}\hfill \end{array}\phantom{\}}$$
Where CD is the angiographic image, M is the magnitude, $\overrightarrow{V}$ is the velocity as determined from phase processing, and V_A is an arbitrarily defined threshold velocity. This weighting scheme mimics complex difference processing (22 (link)), but allows use of balanced 4-point imaging and phase difference processing. For all reconstructed images reported here, V_A was set to the VENC of 60 cm/s.
A standard quality assurance phantom was imaged for the evaluation of off-resonance and trajectory corrections. Magnitude phantom images were reconstructed without off-resonance or trajectory corrections, with off-resonance corrections, with trajectory corrections, and with both trajectory and off-resonance corrections. These images were then qualitatively evaluated for image distortions and artifacts as compared to the known geometry.
Subsequently, five normal volunteers and five patients with known arteriovenous malformations (AVM) were examined with institutional board approval and informed patient consent for an in-vivo assessment of the extended PC VIPR acquisition technique. Image quality comparisons were made, examining background suppression, edge sharpness and vessel visualization, between corrected (off-resonance + trajectory) and uncorrected angiographic images by 2 board certified, blinded readers, with criteria defined in Table 1. Edge sharpness and background suppression were evaluated over the entire volume, while vessel visualization was evaluated individually on the carotids, middle cerebral arteries (MCA), anterior cerebral/communication arteries (ACA/ACOMM), vertebral (VERT), and posterior cerebral arties (PCA). Statistical significance of differences in scores was determined using a Friedman test (n=5) for each category and across observers using both patient an volunteer populations. The significance image quality differences between volunteer and patient populations were determined using a Friedman test (n=5) of corrected images, across all categories.