Cerebral blood flow threshold of ischemic penumbra and infarct core in acute ischemic stroke: a systematic review.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to Ting-Yim Lee.
Explore the source record for details and available documents.
PURPOSE: To prospectively determine the relationship between hepatic tumor blood flow and glucose utilization in vivo by using a combined positron emission tomographic (PET)/computed tomographic (CT) scanner. MATERIALS AND METHODS: The animal care and use subcommittee at the University of Western Ontario approved this study. VX2 carcinoma cells were implanted in the livers of eight male New Zealand white rabbits. Functional CT was performed before tumor implantation and every 4 days thereafter. Each examination consisted of two phases: In the first phase, 30-second cine breath-hold scanning was performed with simultaneous injection of 5 mL of contrast material. In the second phase, 4-second cine scanning was performed without breath holding every 10 seconds for 2 minutes. Second-phase CT images were coregistered with first-phase images to eliminate breathing artifacts. The weighted summation of the aortic and portal venous time-attenuation curves was deconvolved against curves from the liver to derive hepatic blood flow (HBF). Five animals underwent fluorine 18 fluorodeoxyglucose (FDG) scanning before and every 8 days after implantation. FDG uptake was measured as standardized uptake value (SUV). Data were analyzed with repeated-measures analysis of variance and the Tukey-Kramer multiple comparison test. Linear regression was used to compare SUV and HBF in tumors and normal tissue. RESULTS: In the hypovascular tumor core, (a) mean HBF decreased from 262 mL.min-1.100 g-1+/-22 (standard deviation) at baseline to 101 mL.min-1.100 g-1+/-62 at the end of the study (P<.05) and (b) mean SUV increased from 2.12 g/mL+/-0.06 to 4.56 g/mL+/-0.73 (P<.05) during the same period. CONCLUSION: Functional CT in combination with FDG PET can be used to observe changes in HBF and glucose utilization in a growing liver tumor.
Explore the source record for details and available documents.
Predicting the onset of secondary energy failure after a hypoxic-ischemic insult in newborns is critical for providing effective treatment. Measuring reductions in the cerebral metabolic rate of oxygen (CMRO(2)) may be one method for early detection, as hypoxia-ischemia is believed to impair oxidative metabolism. We have developed a near-infrared spectroscopy (NIRS) technique based on the Fick Principle for measuring CMRO(2). This technique combines cerebral blood flow (CBF) measurements obtained using the tracer indocyanine green with measurements of the cerebral deoxy-hemoglobin (Hb) concentration. In this study, NIRS measurements of CMRO(2) were compared with CMRO(2) determined from the product of CBF and the cerebral arteriovenous difference in oxygen measured from blood samples. The blood samples were collected from a peripheral artery and the sagittal sinus. Eight piglets were subjected to five cerebral metabolic states created by varying the plane of anesthesia. No significant difference was found between CMRO(2) measurements obtained with the two techniques at any anesthetic level (P>0.5). Furthermore, there was a strong correlation when concomitant CMRO(2) values from the two techniques were compared (R(2)=0.88, P<0.001). This work showed that CMRO(2) can be determined accurately by combining NIRS measurements of CBF and Hb. Since NIRS is safe and measurements can be obtained at the bedside, it is believed that this technique could assist in the early diagnosis of cerebral energy dysfunction after hypoxia-ischemia.
Impaired oxidative metabolism following hypoxia-ischemia (HI) is believed to be an early indicator of delayed brain injury. The cerebral metabolic rate of oxygen (CMRO2) can be measured by combining near-infrared spectroscopy (NIRS) measurements of cerebral blood flow (CBF) and cerebral deoxy-hemoglobin concentration. The ability of NIRS to measure changes in CMRO2 following HI was investigated in newborn piglets. Nine piglets were subjected to 30 min of HI by occluding both carotid arteries and reducing the fraction of inspired oxygen to 8%. An additional nine piglets served as sham-operated controls. Measurements of CBF, oxygen extraction fraction (OEF), and CMRO2 were obtained at baseline and at 6 h after the HI insult. Of the three parameters, only CMRO2 showed a persistent and significant change after HI. Five minutes after reoxygenation, there was a 28+/-12% (mean+/-SE) decrease in CMRO2, a 72+/-50% increase in CBF, and a 56+/-19% decrease in OEF compared with baseline (P<0.05). By 30 min postinsult and for the remainder of the study, there were no significant differences in CBF and OEF between control and insult groups, whereas CMRO2 remained depressed throughout the 6-h postinsult period. This study demonstrates that NIRS can measure decreases in CMRO2 caused by HI. The results highlight the potential for NIRS to be used in the neonatal intensive care unit to detect delayed brain damage.
PURPOSE: To use first-pass perfusion computed tomography (CT) to prospectively investigate tumor vascularity in rectal cancer and to determine whether any of the perfusion parameters would predict tumor response to chemotherapy and radiation therapy. MATERIALS AND METHODS: The institutional review board approved this study, and informed prior consent was obtained from participants. Perfusion CT of rectal cancer was performed with four-section multi-detector row CT in 15 patients (13 men, two women; mean age, 62.1 years; age range, 46-84 years). Five patients with prostate cancer served as controls. All patients with rectal cancer underwent 6-8 weeks of chemotherapy and radiation therapy followed by surgery. In nine patients, perfusion CT was repeated after completion of chemotherapy and radiation therapy. Contrast medium-enhanced dynamic CT was performed with a static table position for 45 seconds, and the data were analyzed by using commercial software to calculate tissue blood flow (BF), blood volume, mean transit time (MTT), and vascular permeability-surface area product. Perfusion parameters of normal rectum and tumor were compared. Perfusion parameters before and after chemotherapy and radiation therapy were compared. A tumor was considered to have responded if its stage at pathologic analysis indicated regression compared with the preoperative stage. Baseline perfusion values were compared between responders and nonresponders. Statistical analysis was performed with the Student t test. RESULTS: Rectal cancer showed higher BF and shorter MTT compared with those of normal rectum (P < or =.05). After chemotherapy and radiation therapy, tumors showed significant reduction in BF and increase in MTT (P < or =.05). There was a significant difference in baseline BF and MTT values between responders and nonresponders (P < or =.05). Tumors in three patients with high initial BF and short MTT showed poor response. CONCLUSION: Perfusion CT of rectal cancer can enable assessment of tumor vascularity and perfusion changes that result from chemotherapy and radiation therapy. In this small patient sample, tumors with initial high BF and short MTT values tended to respond poorly to chemotherapy and radiation therapy.
Explore the source record for details and available documents.
We compared subcutaneous and oral methods of nimodipine administration to determine a method of nimodipine administration that maintained serum levels at or above the optimal therapeutic concentration (7 ng/ml). Plasma concentrations of nimodipine were measured in New Zealand White rabbits (2.6-3.9 kg). First, peak plasma concentration (C(max)), time to reach peak plasma concentration (T(max)), and area under the curve (AUC) parameters were calculated and compared between animals receiving oral or subcutaneous nimodipine (5-15 mg/kg). Next, plasma concentrations were measured 24 h after subcutaneous administration of 2.5 mg/kg of nimodipine in healthy animals and animals with experimentally induced SAH. C(max), T(max) and AUC parameters were significantly greater for subcutaneous compared to oral nimodipine administration, irrespective of dose. Mean nimodipine concentrations at 24 h were >7 ng/ml in both healthy animals (12.9 +/- 10.0 ng/ml) and in animals with SAH (11.8 +/- 4.6 ng/ml) that received 2.5 mg/kg of subcutaneous nimodipine. In this model, the subcutaneous method of nimodipine administration consistently maintains plasma levels at or above the optimal therapeutic concentration, whereas oral administration fails to do so.
With recent discussions in the literature regarding prophylactic use of early (within the first 12 h after birth), low-dose indomethacin to reduce the incidence and severity of intraventricular hemorrhage, knowledge pertaining to the cerebral hemodynamic effects of indomethacin in this age group is of significant interest. The cerebral circulation is known to undergo significant changes during the first few days of postnatal life. In the present study, we have investigated the hypothesis that postnatal adaptive changes influence the cerebral hemodynamic response to indomethacin in an age-dependent manner. Near-infrared spectroscopy with indocyanine green was used to measure cerebral hemodynamics, cerebral metabolic rate of oxygen, and cerebral oxygen extraction fraction in 39 newborn piglets. Piglets were grouped by age and received either 0.2 mg/kg indomethacin (14 were <13 h of age and 12 were >13 h of age) or saline (8 were <13 h of age and 5 were >13 h of age) infusions. In a subgroup of indomethacin-treated piglets (9 less than and 7 greater than 13 h of age), Doppler flow ultrasound was used to diagnose and monitor the presence and persistence of patent ductus arteriosus. Age was a significant factor in the cerebral hemodynamic response to indomethacin with piglets <13 h of age exhibiting delayed increases in cerebral blood flow and cerebral blood volume at 150 min post-indomethacin infusion.
Changes in T2*-weighted tissue sodium (23Na) signal following acute ischemia may help to identify necrotic tissue and estimate the duration of ischemia. Sodium signal was monitored in a rabbit model of acute (0-4 h) focal cerebral ischemia, using gradient echo 23Na MR images (echo time = 3.2 ms) acquired continuously in 20-min intervals on a 4-Tesla MRI. 2,3,5-Triphenyl-tetrazolium chloride staining was used to identify regions of necrosis. In necrotic tissue, average 23Na image signal intensity decreased by 11% +/- 8% during the first 40 min of ischemia followed by a linear increase (0.19%/min) to 25% +/- 14% greater than baseline after 4 h of ischemia. The time course of 23Na signal change observed in necrotic tissue following focal ischemia in this rabbit model is consistent with an initial decrease in 23Na T2* relaxation time followed by an increase in tissue sodium concentration and provides further evidence that tissue 23Na signal may offer unique information regarding tissue viability that is complementary to other MR imaging techniques.
RATIONALE AND OBJECTIVES: The aim was to evaluate functional computed tomography (fCT) in the quantification of angiogenesis by comparing the tissue perfusion parameters measured by CT perfusion (CTP) software with histologic vascular parameters in a Matrigel model in rats. It was hypothesized that tissue perfusion parameters and histologic vascular parameters are related. MATERIALS AND METHODS: In vivo angiogenesis assays were performed using Matrigel supplemented with escalating doses (0 ng [control group], 250 ng, and 1,000 ng) of recombinant rat vascular endothelial growth factor (VEGF164) subcutaneously injected into the backs of Sprague Dawley rats. On day 7, rats with Matrigel plug underwent fCT following a bolus injection of iodinated contrast medium. Using CTP software, fCT parameters were generated (blood flow [BF], blood volume [BV], mean transit time, and permeability-surface area product) and functional maps on the basis of a distributed parameter tracer kinetic model, the adiabatic approximation to the tissue homogeneity model. The animals were then sacrificed. Matrigel plug was sectioned into slices corresponding to the CT scan plane and stained with CD31 immunohistochemical stain. Histologic vascular parameters, including microvascular density (MVD), vessel number (VN), vascular area, and vascular perimeter, were measured. CTP and histologic parameters were correlated. RESULTS: The Matrigel plugs with the 1,000-ng VEGF group exhibited a higher MVD than the 250-ng VEGF and control groups (P < .05). VN differed significantly between the control versus the 250-ng VEGF groups and 250-ng versus 1,000-ng VEGF groups (P < .05), with the highest VN in the 250-ng VEGF group. BF, mean transit time, and permeability-surface area product each differed significantly to VEGF levels. Changes in BF and BV did not correspond with increases in MVD or VN; however, in the 250-ng VEGF group, there was a strong positive correlation (r = 0.9) between BV and VN, vascular area, and vascular perimeter, which was not seen in the control or 1,000-ng VEGF group. All fCT parameters significantly correlated with each other (P < .05), with strong correlations between BF and mean transit time (r = -0.7) and between BF and permeability-surface area product (r = 0.7) and a weak correlation between BF and BV (r = 0.3). CONCLUSION: These results validate the VEGF-induced endothelial cell in a rat Matrigel model. In addition, histologic vascular parameter MVD does not correlate with fCT parameters measured by CTP software.
We propose a new scanning protocol for generating 4D-CT image data sets influenced by respiratory motion. A cine scanning protocol is used during data acquisition, and two registration methods are used to sort images into temporal phases. A volume is imaged in multiple acquisitions of 1 or 2 cm length along the cranial-caudal direction. In each acquisition, the scans are continuously acquired for a time interval greater than or equal to the average respiratory cycle plus the duration of the data for an image reconstruction. The x ray is turned off during CT table translation and the acquisition is repeated until the prescribed volume is completely scanned. The scanning for 20 cm coverage takes about 1 min with an eight-slice CT or 2 mins with a four-slice CT. After data acquisition, the CT data are registered into respiratory phases based on either an internal anatomical match or an external respiratory signal. The internal approach registers the data according to correlation of anatomy in the CT images between two adjacent locations in consecutive respiratory cycles. We have demonstrated the technique with ROIs placed in the region of diaphragm. The external approach registers the image data according to an externally recorded respiratory signal generated by the Real-Time Position Management (RPM) Respiratory Gating System (Varian Medical Systems, Palo Alto, CA). Compared with previously reported prospective or retrospective imaging of the respiratory motion with a single-slice or multi-slice CT, the 4D-CT method proposed here provides (1) a shorter scan time of three to six times faster than the single-slice CT with prospective gating; (2) a shorter scan time of two to four times improvement over a previously reported multi-slice CT implementation, and (3) images over all phases of a breathing cycle. We have applied the scanning and registration methods on phantom, animal and patients, and initial results suggest the applicability of both the scanning and the registration methods.
Cerebral metabolic rate of oxygen (CMRO2), the rate at which O2 is consumed in the brain by metabolic processes, is one of the most useful measures of normal brain function. The present study investigated the use of near-infrared spectroscopy (NIRS) in the noninvasive measurement of O2 extraction fraction (OEF) and CMRO2 in the newborn piglet. Indomethacin, although used successfully to effect closure of patent ductus arteriosus in the preterm infant, is known to cause transient reductions in cerebral blood flow (CBF) in both infant and adult humans and pigs. As a test of the NIRS method, the present study also examined the effect of indomethacin-induced reductions in CBF on both OEF and CMRO2. CBF, OEF, and CMRO2 were assessed in 20 newborn piglets, 0.2-3.0 d old. Ten piglets received 0.2 mg/kg of indomethacin infused over 30 min; remaining piglets received saline infusion as control. CBF, OEF, and CMRO2 measurements were performed before infusion and at 30-min intervals for a period of 90 min post-infusion. Saline infusion elicited no response in CBF, OEF, or CMRO2. Immediately after indomethacin infusion, CBF decreased 18.1% below (p < 0.05) and OEF increased 26.2% above (p < 0.05) pre-infusion values, whereas CMRO2 showed no significant changes throughout the study. Both CBF and OEF returned to baseline within 60 min after infusion of indomethacin. The proficiency of NIRS in the measurement of OEF and CMRO2 was demonstrated through the observation of transient increases in OEF, which served to maintain CMRO2 during indomethacin-induced reductions in CBF.
Tumour blood flow is one of the important factors limiting the efficacy of radiation therapy (hypoxic radioresistance), chemotherapy (drug delivery) and thermal therapy (heat dissipation) in treating cancer. The modification of tumour blood flow has been an area of intense investigation. In the current study, the arterial carbon dioxide tension (PaCO2) was changed in order to investigate the tumour vascular response to carbon dioxide. Functional maps of blood flow, blood volume and mean transit time were generated at four PaCO2 levels in VX2 tumour in the rabbit thigh and normal soft tissue. The PaCO2 levels investigated were normocapnia (PaCO2 = 40.9 +/- 1.2 mmHg), hypocapnia (27.2 +/- 2.3 and 33.5 +/- 2.3 mmHg) and hypercapnia (54.9 +/- 4.4 mmHg). The carbon dioxide reactivity of the global tumour blood flow and mean transit time showed significant differences between normocapnia and the two levels of hypocapnia, but not between normocapnia and hypercapnia. The average fractional change of blood flow from normocapnia for the two levels of hypocapnia was -0.41 +/- 0.06 and -0.29 +/- 0.08, respectively (P < 0.05). In the case of mean transit time the fractional change was +0.39 +/- 0.30 and +0.23 +/- 0.24, respectively (P < 0.05). The fractional change of blood volume from normocapnia, however, was not significantly different at any capnic level, as was the case with respect to each of the functional parameters in normal tissue. The ability to reduce blood flow and increase mean transit time through hypocapnia has significant implications in thermal therapy, since heat dissipation is a major factor in limiting the effectiveness of treatment.
A computed tomography (CT) perfusion imaging and a diffusion/perfusion magnetic resonance imaging (MRI) were performed in a 51-year-old man at 15 and 15.5 h of onset of left middle cerebral artery infarction, respectively. The established infarct, as revealed by the diffusion-weighted MRI, had low values of cerebral blood flow (CBF) and cerebral blood volume (CBV) on the CT perfusion study. The ischaemic penumbra, as reflected by the perfusion-diffusion mismatch on MRI, had reduced CBF, prolonged mean transit time (MTT) and compensated CBV. Spontaneous bleeding occurred in the medial part of the left lentiform nucleus, immediately following decompressive craniectomy. CT measurements of CBF, CBV and MTT may visualize the ischaemic penumbra and explain the site of bleeding after surgical decompression.
BACKGROUND AND PURPOSE: Compared with MR imaging, dynamic CT perfusion imaging covers only a fraction of the whole brain. An important assumption is that CT perfusion abnormalities correlate with total ischemic volume. The purpose of our study was to measure the degree of correlation between abnormalities seen on CT perfusion scans and the volumes of abnormality seen on MR diffusion and perfusion images in patients with acute large-vessel stroke. METHODS: Fourteen patients with acute hemispheric stroke symptoms less than 12 hours in duration were studied with single-slice CT perfusion imaging and multislice MR diffusion and perfusion imaging. CT and MR perfusion studies were completed within 2.5 hours of one another (mean, 77 minutes) and were reviewed independently by two neuroradiologists. Hemodynamic parameters included cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Extents of abnormality on images were compared by using Kendall correlation. RESULTS: Statistically significant correlation was found between CT-CBF and MR-CBF abnormalities (tau = 0.60, P =.003) and CT-MTT and MR-MTT abnormalities (tau = 0.65, P =.001). Correlation of CT-CBV with MR-CBV approached significance (tau = 0.39, P =.06). Extent of initial hyperintensity on diffusion-weighted images correlated best with extent of MR-CBV abnormality (tau = 0.69, P =.001), extent of MR-MTT abnormality (tau = 0.67, P =.002), and extent of CT-CBV abnormality (tau = 0.47, P =.02). CONCLUSION: Good correlation was seen between CT and MR for CBF and MTT abnormalities. It remains uncertain whether CT perfusion CBV abnormalities correspond well to whole-brain abnormalities.
Explore the source record for details and available documents.
UNLABELLED: Using computerized tomography, we measured absolute cerebral blood flow (CBF) and cerebral blood volume (CBV) in tumor, peri-tumor, and contralateral normal regions, at normocapnia and hypocapnia, in 16 rabbits with brain tumors (VX2 carcinoma), under isoflurane or propofol anesthesia. In both anesthetic groups, CBV and CBF were highest in the tumor region and lowest in the contralateral normal tissue. For isoflurane, a significant decrease in both CBV and CBF was observed in all tissue regions with hyperventilation (P < 0.05), but without accompanying changes in intracranial pressure. However, the percent reduction in regional CBF with hypocapnia was two times larger than that observed in the CBV response (P < 0.01). In contrast, there were no significant changes in CBV and CBF in the Propofol group with hyperventilation for all regions (P > 0.10). In addition, there were no differences between CBV values for isoflurane at hypocapnia when compared with CBV values for propofol at normo- or hypocapnia (P > 0.34 and P > 0.35, respectively, in the tumor regions). Our results indicate that propofol increases cerebral vascular tone in both neoplastic and normal tissue vessels compared with isoflurane. CBV and CBF during normocapnia were significantly greater in all regions (tumor, peri-tumor, and contralateral normal tissue) with isoflurane than with propofol. CBV and CBF remained responsive to hyperventilation only with isoflurane. IMPLICATIONS: In rabbits with brain tumors, brain blood flow and volume were significantly larger in all regions (tumor, peri-tumor, and contralateral normal tissue) with isoflurane than with propofol during normocapnia, and remained responsive to a reduction in PaCO(2). Consequently, during hypocapnia, brain blood flow and volume values with isoflurane were similar to values with propofol.