Ting-Yim Lee

Identification of Penumbra and Infarct in Acute Ischemic Stroke Using Computed Tomography Perfusion–Derived Blood Flow and Blood Volume Measurements

Background and Purpose— We investigated whether computed tomography (CT) perfusion–derived cerebral blood flow (CBF) and cerebral blood volume (CBV) could be used to differentiate between penumbra and infarcted gray matter in a limited, exploratory sample of acute stroke patients. Methods— Thirty patients underwent a noncontrast CT (NCCT), CT angiography (CTA), and CT perfusion (CTP) scan within 7 hours of stroke onset, NCCT and CTA at 24 hours, and NCCT at 5 to 7 days. Twenty-five patients met the criteria for inclusion and were subsequently divided into 2 groups: those with recanalization at 24 hours (n=16) and those without (n=9). Penumbra was operationally defined as tissue with an admission CBF <25 mL · 100 g−1 · min−1 that was not infarcted on the 5- to 7-day NCCT. Logistic regression was applied to differentiate between infarct and penumbra data points. Results— For recanalized patients, CBF was significantly lower (P<0.05) for infarct (13.3±3.75 mL · 100 g−1 · min−1) than penumbra (25.0±3.82 mL · 100 g−1 · min−1). CBV in the penumbra (2.15±0.43 mL · 100 g−1) was significantly higher than contralateral (1.78±0.30 mL · 100 g−1) and infarcted tissue (1.12±0.37 mL · 100 g−1). Logistic regression using an interaction term (CBF×CBV) resulted in sensitivity, specificity, and accuracy of 97.0%, 97.2%, and 97.1%, respectively. The interaction term resulted in a significantly better (P<0.05) fit than CBF or CBV alone, suggesting that the CBV threshold for infarction varies with CBF. For patients without recanalization, CBF and CBV for infarcted regions were 15.1±5.67 mL · 100 g−1 · min−1 and 1.17±0.41 mL · 100 g−1, respectively. Conclusions— We have shown in a limited sample of patients that CBF and CBV obtained from CTP can be sensitive and specific for infarction and should be investigated further in a prospective trial to assess their utility for differentiating between infarct and penumbra.

Functional CT: physiological models

Abstract Since its introduction three decades ago, computed tomography (CT) has been regarded as an imaging technique that is good at providing structural information but poor at providing physiological (functional) data to help with diagnosis. For instance, although it can reveal an abnormal mass present in the lung or liver, it cannot always differentiate a benign mass from a malignant growth. The introduction of fast CT scanners in the past decade, together with the development of better analysis techniques, has helped to launch functional CT as a new method to investigate the physiological basis of function and disease in the human body.

Calibration of diffuse correlation spectroscopy with a time-resolved near-infrared technique to yield absolute cerebral blood flow measurements

A primary focus of neurointensive care is the prevention of secondary brain injury, mainly caused by ischemia. A noninvasive bedside technique for continuous monitoring of cerebral blood flow (CBF) could improve patient management by detecting ischemia before brain injury occurs. A promising technique for this purpose is diffuse correlation spectroscopy (DCS) since it can continuously monitor relative perfusion changes in deep tissue. In this study, DCS was combined with a time-resolved near-infrared technique (TR-NIR) that can directly measure CBF using indocyanine green as a flow tracer. With this combination, the TR-NIR technique can be used to convert DCS data into absolute CBF measurements. The agreement between the two techniques was assessed by concurrent measurements of CBF changes in piglets. A strong correlation between CBF changes measured by TR-NIR and changes in the scaled diffusion coefficient measured by DCS was observed (R2 = 0.93) with a slope of 1.05 ± 0.06 and an intercept of 6.4 ± 4.3% (mean ± standard error).

Comparison of time-resolved and continuous-wave near-infrared techniques for measuring cerebral blood flow in piglets.

A primary focus of neurointensive care is monitoring the injured brain to detect harmful events that can impair cerebral blood flow (CBF), resulting in further injury. Since current noninvasive methods used in the clinic can only assess blood flow indirectly, the goal of this research is to develop an optical technique for measuring absolute CBF. A time-resolved near-infrared (TR-NIR) apparatus is built and CBF is determined by a bolus-tracking method using indocyanine green as an intravascular flow tracer. As a first step in the validation of this technique, CBF is measured in newborn piglets to avoid signal contamination from extracerebral tissue. Measurements are acquired under three conditions: normocapnia, hypercapnia, and following carotid occlusion. For comparison, CBF is concurrently measured by a previously developed continuous-wave NIR method. A strong correlation between CBF measurements from the two techniques is revealed with a slope of 0.79±0.06, an intercept of -2.2±2.5 ml∕100 g∕min, and an R2 of 0.810±0.088. Results demonstrate that TR-NIR can measure CBF with reasonable accuracy and is sensitive to flow changes. The discrepancy between the two methods at higher CBF could be caused by differences in depth sensitivities between continuous-wave and time-resolved measurements.

Quantitative measurement of cerebral blood flow in a juvenile porcine model by depth-resolved near-infrared spectroscopy

Nearly half a million children and young adults are affected by traumatic brain injury each year in the United States. Although adequate cerebral blood flow (CBF) is essential to recovery, complications that disrupt blood flow to the brain and exacerbate neurological injury often go undetected because no adequate bedside measure of CBF exists. In this study we validate a depth-resolved, near-infrared spectroscopy (NIRS) technique that provides quantitative CBF measurement despite significant signal contamination from skull and scalp tissue. The respiration rates of eight anesthetized pigs (weight: 16.2+/-0.5 kg, age: 1 to 2 months old) are modulated to achieve a range of CBF levels. Concomitant CBF measurements are performed with NIRS and CT perfusion. A significant correlation between CBF measurements from the two techniques is demonstrated (r(2)=0.714, slope=0.92, p<0.001), and the bias between the two techniques is -2.83 mL min(-1)100 g(-1) (CI(0.95): -19.63 mL min(-1)100 g(-1)-13.9 mL min(-1)100 g(-1)). This study demonstrates that accurate measurements of CBF can be achieved with depth-resolved NIRS despite significant signal contamination from scalp and skull. The ability to measure CBF at the bedside provides a means of detecting, and thereby preventing, secondary ischemia during neurointensive care.

Quantitative myocardial CT perfusion: a pictorial review and the current state of technology development

Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality, and is associated with substantial and increasing resource burden. A combined physiologic and anatomic assessment may improve identification of patients with CAD who would benefit from revascularization and reduce unnecessary diagnostic and interventional procedures. Cardiovascular computed tomography (CT) has the potential to provide a comprehensive evaluation of CAD in a single setting. Although coronary CT angiography has been widely implemented for clinical use, the application of myocardial CT perfusion (CTP) has been relatively restricted because of a few limitations, such as beam hardening and the high radiation dose delivered. In this article, we first review the fundamental basis of the qualitative, semiquantitative, and quantitative techniques for myocardial CTP and discussed the strength and weakness of each approach. Beam-hardening correction for myocardial CTP with image-based method and dual-energy CT are then discussed with example cases demonstrating the effectiveness of each method. Initial experiences suggest both techniques can reduce beam-hardening artifact to a satisfactory extent. An overview on dose reduction technologies, such as prospective ECG triggering and iterative reconstruction for myocardial CTP, is also provided. Preclinical studies suggest it is feasible to perform low-dose quantitative myocardial CTP without affecting perfusion measurement. Finally, the impact of scan length on myocardial CTP is addressed.

A broadband continuous-wave multichannel near-infrared system for measuring regional cerebral blood flow and oxygen consumption in newborn piglets.

Near-infrared spectroscopy (NIRS) is a promising technique for assessing brain function in newborns, particularly due to its portability and sensitivity to cerebral hemodynamics and oxygenation. Methods for measuring cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) have been developed based on broadband continuous-wave NIRS. However, broadband NIRS apparatus typically have only one detection channel, which limits their applicability to measuring regional CBF and CMRO(2). In this study, a relatively simple multiplexing approach based on electronically controlled mechanical shutters is proposed to expand the detection capabilities from one to eight channels. The tradeoff is an increase in the sampling interval; however, this has negligible effects on CBF measurements for intervals less than or equal to 1 s. The ability of the system to detect focal brain injury was demonstrated in piglets by injecting endothelin-1 (ET-1) into the cerebral cortex. For validation, CBF was independently measured by computed tomography (CT) perfusion. The average reduction in CBF from the source-detector pair that interrogated the injured region was 51%+/-9%, which was in good agreement with the CBF reduction measured by CT perfusion (55%+/-5%). No significant changes in regional CMRO(2) were observed. The average regional differential pathlength prior to ET-1 injection was 8.4+/-0.2 cm (range of 7.1-9.6 cm) and did not significantly change after the injury.

Broadband continuous-wave technique to measure baseline values and changes in the tissue chromophore concentrations

We present a broad-band, continuous-wave spectral approach to quantify the baseline optical properties of tissue and changes in the concentration of a chromophore, which can assist to quantify the regional blood flow from dynamic contrast-enhanced near-infrared spectroscopy data. Experiments were conducted on phantoms and piglets. The baseline optical properties of tissue were determined by a multi-parameter wavelength-dependent data fit of a photon diffusion equation solution for a homogeneous medium. These baseline optical properties were used to find the changes in Indocyanine green concentration time course in the tissue. The changes were obtained by fitting the dynamic data at the peak wavelength of the chromophore absorption, which were used later to estimate the cerebral blood flow using a bolus tracking method.

Assessment of the best flow model to characterize diffuse correlation spectroscopy data acquired directly on the brain.

Diffuse correlation spectroscopy (DCS) is a non-invasive optical technique capable of monitoring tissue perfusion. The normalized temporal intensity autocorrelation function generated by DCS is typically characterized by assuming that the movement of erythrocytes can be modeled as a Brownian diffusion-like process instead of by the expected random flow model. Recently, a hybrid model, referred to as the hydrodynamic diffusion model, was proposed, which combines the random and Brownian flow models. The purpose of this study was to investigate the best model to describe autocorrelation functions acquired directly on the brain in order to avoid confounding effects of extracerebral tissues. Data were acquired from 11 pigs during normocapnia and hypocapnia, and flow changes were verified by computed tomography perfusion (CTP). The hydrodynamic diffusion model was found to provide the best fit to the autocorrelation functions; however, no significant difference for relative flow changes measured by the Brownian and hydrodynamic diffusion models was observed.

The effect of an inconsistent breathing amplitude on the relationship between an external marker and internal lung deformation in a porcine model

PURPOSEnInvestigate the relationship between the motion of the Varian Real-time Position Management (RPM) device and the internal motion of a pig during induced inconsistencies in the amplitude of breathing.nnnMETHODSnTwelve studies were performed on four ventilated female Landrace cross pigs using a GE Healthcare, Discovery CT 750 HD scanner. In each study, a 4.0 cm section (64 slices) of the pigs lungs was repeatedly scanned 20 times using cine mode, each time lasting more than one breathing cycle. During these cine scans, a Varian RPM device was used to collect respiratory amplitudes and the ventilator air return tube was periodically crimped to induce inconsistent breathing amplitudes. Each breathing cycle and its associated cine scan were categorized as either consistent or inconsistent, based on thresholds of the minimum expiration and maximum inspiration amplitudes. From the group of consistent amplitude cine scans in a study, a reference scan was chosen. The effect of inconsistent breathing amplitudes on the relationship between the motion of the RPM marker and the motion within three regions of interest (in each lung and the chest wall) was investigated with two methods: (1) A 4D-CT sorting algorithm based on RPM amplitude was used to sort volumes into 4D-CT phase bins. Within each phase bin, the nonlinear deformation of volumes collected during consistent and inconsistent breathing amplitude was calculated with respect to the reference volume. The magnitude of the deformations (in mm) were compared to determine if inconsistent breathing amplitude caused greater deformations. (2) Nonlinear deformations between each CT volume from a cine scan and the maximum expiration volume of the reference scan were calculated. Regression analyses between the nonlinear deformations within three regions of interest (in each lung and the chest wall) and the RPM amplitudes were performed to test the effect of inconsistent breathing amplitudes on the linearity of the relationship between the 3D motion of internal anatomy and the 1D motion of the RPM external marker.nnnRESULTSn(1) Inconsistent versus consistent breathing amplitudes caused a significant increase in deformation relative to the reference scan within the left lung (1.40 +/- 0.42 versus 1.29 +/- 0.36 mm, p < 0.05). (2) One-to-one correspondences between motions of internal anatomies and motion of the RPM external marker did not exist. The regression lines between the two types of motions did not yield an identity relationship (unity slope and zero intercept). Inconsistent breathing produced significantly different regression lines than consistent breathing in ten of the 12 studies within a left lung region of interest.nnnCONCLUSIONSnThe results of these two studies indicate that inconsistency in the amplitude of breathing disrupted the correspondence between the motion of the external marker and internal anatomies. As a consequence, radiation therapy of tumors embedded in lung tissue may be prone to significant errors if inconsistent breathing amplitudes occur during treatment.