Accuracy of Dynamic Perfusion CT with Deconvolution in Detecting Acute Hemispheric Stroke

Design

Imaging data obtained as part of standard clinical stroke care at our institution were retrospectively reviewed with the approval of our institutional review board. At our institution, patients with suspected acute stroke and no notable renal insufficiency or allergy to contrast agent undergo the following imaging protocol: nonenhanced CT, PCT at two cross-sectional positions, CTA of the cervical and intracranial vessels, and contrast-enhanced cerebral CT (15). The acquisition parameters for the PCT series are described later.

Nonenhanced CT and PCT data were included in this study if these conditions were met: 1) The patient presented to the emergency department with signs and symptoms suggestive of hemispheric stroke (e.g., hemisensory loss, hemiparesis, aphasia, or homonymous visual field abnormality) of 12 hours’ duration or less, 2) there was no evidence of intracerebral hemorrhage, and 3) the patient underwent follow-up CT or MR imaging to confirm or rule out ischemic hemispheric stroke. Patients who underwent thrombolysis were excluded.

Imaging Protocol

PCT consisted of a 45-second series with 45 gantry rotations performed in cine mode during the intravenous administration of iodinated contrast material. Images were acquired and reconstructed at a temporal sampling rate of one image per second, resulting in a series of 45 images for each assessed section. Two successive PCT series were performed after nonenhanced CT and before CTA. The two PCT series were separated by 5 minutes.

Multidetector-row CT technology permitted the assessment of two adjacent 10-mm-thick sections for each series. Two 10-mm-thick sections were preferred to four adjacent 5-mm-thick sections per location to maximize the signal-to-noise ratio without increasing the dose to the patient. The two sections of the first PCT series were at the level of the third ventricle and the basal ganglia, positioned above the orbits to protect the lenses. The second PCT series was selected at a level 3.5 cm rostral to the first section of the first series.

For each series, a 40-mL bolus of iohexol (Omnipaque, iodine 300 mg/mL; Amersham Health, Princeton, NJ) was administered into an antecubital vein by using a power injector at an injection rate of 4 mL/s. The acquisition parameters were 80 kVp and 120 mAs. CT scanning was initiated 7 seconds after the start of the injection. The time delay before contrast material reached the brain parenchyma allowed the acquisition of nonenhanced baseline images.

Data Processing

PCT data were analyzed by using PCT prototype software (Philips Medical Systems, Best, the Netherlands). This software relies on the central volume principle, which is the most accurate for low injection rates of iodinated contrast material (6). After motion correction and noise reduction are done by using an anisotropic, edge-preserving spatial filter, the software applies curve fitting by a least-mean-squares method to obtain mathematical descriptions of the time-attenuation curves. Then, it applies a closed-form (noniterative) deconvolution to calculate the MTT map (17). The deconvolution operation requires a reference arterial input function, which selected by the PCT software in a region of interest that the user draws around the anterior cerebral artery (ACA). The rCBV map is calculated from the areas under the time-enhancement curves (18). A simple equation combining rCBV and MTT values allows the calculation of rCBF: rCBF = rCBV/MTT (17). Finally, the software calculates an automated computerized map of the penumbra and infarct by using rCBF and rCBV thresholds, according to a method previously described and validated (13, 14).

Data Analysis

Two observers (a neuroradiologist [W.P.D.] and a stroke neurologist [W.S.S.]) reviewed each of the 46 nonenhanced CT studies obtained on admission. They evaluated the images for conventional signs of stroke: hemispheric hypoattenuation or swelling, loss of the cortical ribbon (including the insular ribbon), hypoattenuation in the basal ganglia, and the attenuated artery sign. They also assess the studies according to the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) (19) and Alberta Stroke Program Early CT Score (ASPECTS) systems (20). For the ATLANTIS system, the reviewers evaluated hypoattenuation in four areas: frontal, temporal, parietal, and basal ganglia and insular cortex. If two or more areas showed hypoattenuation, the patient was considered to have a stroke involving more than one third of the middle cerebral artery (MCA) territory (19). For the ASPECTS system, the reviewers evaluated hypoattenuation in 10 areas: caudate, lenticulate, internal capsule, insula, M1, M2, M3, M4, M5, and M6. Their assessments lead to a score ranging from 10 (no areas with hypoattenuation) to 0 (10 areas with hypoattenuation). If the score was 7 or less, the patient was considered to have a stroke involving more than one third of the MCA territory (20). Finally, the reviewers assessed hypoattenuation in the arterial territories of the ACA and posterior cerebral artery (PCA).

In separate review sessions, the same reviewers reviewed the rCBV, rCBF, MTT, and time-to-peak (TTP) maps for abnormally low rCBV, low rCBF, high MTT, and high TTP values in the four areas defined in the ATLANTIS method, the 10 areas defined in the ASPECTS method, and the ACA and PCA territories. If two or more areas from the ATLANTIS method or if three or more areas from the ASPECTS method showed abnormal values, the patient was considered to have a stroke involving more than one third of the MCA territory, as shown on the corresponding PCT map. Special attention was paid to the blinding of patient data. Moreover, reviews of the nonenhanced CT scans and rCBV, rCBF, MTT, and TTP maps were performed successively, at 2-week intervals. The reviewers performed the readings independently of each other and were blinded to the other’s opinions, as well as the results of the formal, dictated evaluation of these examinations. The reviewers were informed of only the body side of the signs and symptoms to reproduce the emergency setting as closely as possible.

The reviewers’ assessment of the PCT maps relied on their subjective visual evaluation and involved a comparison of the presumed pathologic hemisphere with the presumed healthy one. The data were also subjected to automated analysis by PCT prototype software (Philips Medical Systems). As mentioned before, this software automatically defines a computerized map of the infarct and penumbra based on thresholds levels of rCBF and rCBV. This computerized automated map was assessed for possible penumbra or infarct in the four ATLANTIS areas, the 10 ASPECTS areas, and the ACA and PCA territories.

Statistical Analysis

In each patient, follow-up CT or MR images were reviewed according to the scheme just described. The results were considered the criterion standard for the calculation of the sensitivity, specificity, and accuracy of hypoattenuation on nonenhanced CT and of rCBV, rCBF, MTT, and TTP abnormalities on PCT. Sensitivity, specificity, and accuracy were calculated for the detection of stroke and also for the assessment of the extent (more or less than one third of the MCA territory).

For each conventional nonenhanced CT sign (erased cortex, erased insula, erased basal nuclei, attenuated artery sign), the sensitivity, specificity, and accuracy were determined depending on whether a final diagnosis of stroke was confirmed or not. Sensitivity, specificity, and accuracy were also calculated for all the conventional nonenhanced CT signs considered together (e.g., the study was considered positive if any of the previously listed signs were present). These global values for nonenhanced CT were used as a reference in Wilcoxon (Mann-Whitney) tests to determine whether the different PCT maps were superior to nonenhanced CT. The significance level was set at .01 to account for the multiple sampling (Bonferroni correction).

Cohen κ coefficients were calculated to determine the interobserver agreement (between the neuroradiologist and the stroke neurologist). These were determined for both the presence and the extent of abnormalities on nonenhanced CT and PCT. A κ value of 0.20 or less implied poor agreement; 0.21–0.40, fair agreement; 0.41–0.60, moderate agreement; 0.61–0.80, substantial agreement; and 0.81–1.00, excellent agreement (21).

Patient Characteristics

Between January and June 2003, 147 patients presented to the emergency department with strokelike symptoms and underwent our stroke CT protocol. Among them, we identified 46 who fulfilled the inclusion criteria. Thirty-one were male and 15 female, with a median age of 64 years (range, 28–94 years). Their symptoms and signs of stroke were left sided in 28 and right sided in 18. The median time between stroke onset and performance of the admission CT protocol was 5.5 hours, with a range of 1.0–12.0 hours. Twenty-nine patients underwent follow-up CT (median, 5 days; range, 3–18 days), and 17 underwent follow-up MR imaging (median, 5 days; range, 2–8 days), which included both DW imaging and fluid-attenuated inversion recovery series. Most patients did not undergo CTA or MR angiography during their follow-up examination. Final diagnoses were acute ischemic stroke in 26 (23 nonlacunar and three lacunar), transient ischemic attack (TIA) in 14, and nonstroke conditions in six (seizures in four, migraine in two). The location of the strokes is summarized in Table 1. Seven patients were also had strokes before the event precipitating the stroke CT protocol.

Nonenhanced CT and PCT in Detecting Stroke

The sensitivity, specificity, accuracy, and interobserver agreement of nonenhanced CT and PCT in the assessment of stroke are summarized in Table 2. The accuracy of PCT was significantly greater than that of nonenhanced CT (75.7–86% vs. 66.2%; P < .01) in the detection of stroke. TTP and MTT maps were significantly more sensitive than nonenhanced CT (76.5% and 77.6%, respectively, vs. 69.2%; P < .01), with a higher interobserver agreement for MTT maps (i.e., 0.618). rCBF and rCBV were significantly more specific then nonenhanced CT (90.9% and 92.7%, respectively, vs. 65.0%; P < .01). On the other hand, interobserver agreement only tended to be better with PCT than with nonenhanced CT. The automated method for delineating brain ischemia had sensitivity, specificity, and accuracy similar to those resulting from the observers’ review; interobserver-agreement issues did not apply, as since it was automated method.

False-Negative and False-Positive Findings

False-negative findings on PCT were related mainly to a lack of spatial coverage. PCT failed to completely reveal a nonlacunar stroke in only one of the 23 patients. In three cases, follow-up imaging demonstrated acute lacunar strokes that were too small to be detected on PCT maps. The other false-negative cases were false-negative areas in patients with true-positive disease (i.e., in each of these patients) PCT demonstrated most but not all ischemic areas. In two cases, hyperemia (high rCBF and rCBV, low MTT and TTP) rather than oligemia was recorded in a territory in which follow-up imaging showed infarct; this led to false-negative results according to the assessment criteria used. This pattern was also identified in three patients with a final diagnosis of TIA; this finding will need to be accounted for in future grading systems. Finally, in four patients, PCT maps were degraded by motion artifacts that compromised the detection of oligemia in some areas; this also led to false-negative results.

One case of arterial recanalization was also documented (Fig 1). In this case, the rCBF, MTT, and TTP maps were abnormal in some areas that were negative for stroke on follow-up examination. The computerized automated map described these areas as penumbra. False-positive results with PCT also occurred in three cases of TIA, in which TTP and MTT maps suggested ischemia (Fig 2). Remote infarctions also led to false-positive results, as they could be distinguished from acute strokes only when PCT maps were interpreted side by side with the corresponding nonenhanced CT.

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Fig 1.

55-year-old man with right homonymous hemianopsia and right-body hemisensory loss. Admission nonenhanced CT 6 hours after symptom onset was unremarkable (both reviewers), except for an attenuated left PCA (arrowheads, one reviewer). PCT shows prolonged MTT and reduced rCBF in the left PCA territory. rCBVs are reduced only in a small part of the left thalamus but are increased in the rest of the PCA territory. The areas correspond to infarct and penumbra on the computerized automated map. Figure and legend continues.

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Fig 1.

Continued.—Admission CTA shows an occluded left P1 segment, which had recanalized but remained focally stenotic on follow-up MR angiography 3 days later. Follow-up DW image shows completed stroke in the predicted left thalamic infarct core. The penumbra did not infarct, most likely because of early recanalization; the MTT and rCBF abnormalities were however, categorized as false-positive since delayed MR imaging was selected as the criterion standard.

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Fig 2.

77-year-old woman with acute-onset left hemiparesis. Admission nonenhanced CT 2 hours after onset is normal. TTP and MTT are prolonged in the right superficial MCA territory (arrows). rCBFs are normal, but rCBVs are higher than contralateral values. TTP and MTT changes are not explained by any vascular abnormality; right carotid bifurcation (arrowhead) and intracranial arteries are normal. Final diagnosis was TIA. Follow-up CT 14 days later was normal. TTP and MTT changes were regarded as false-positive and most likely related to luxury perfusion due to TIA.

Nonenhanced CT and PCT in Assessing Stroke Extent

In assessing the extent of stroke (more or less than one third of the MCA territory), PCT is more sensitive (up to 94.4%), specific (up to 92.1%) and accurate (up to 87.9%) than nonenhanced CT (62.8%). PCT also had significantly increased interobserver agreement. This finding was true with both the ASPECTS (Table 3) and the ATLANTIS scoring systems.