Perfusion harmonic imaging of the human brain

Cerebral cortical blood flow during changes of acid-base equilibrium of the brain.

Objective: To explore the correlation between decreased cerebral perfusion measured from arterial spin labeling and cerebrovascular events in patients with bilateral moyamoya angiography (MMA). Methods: Twenty-seven consecutive cases with bilateral MMA, who were admitted to the neurosurgery department of Nanjing Drum Tower Hospital from April to November 2020, were included in this retrospective study. Among them, 10 were males and 17 were females, aged 35-66 (55±9) years. These patients all presented with unilateral cerebral hemisphere cerebral infarction or cerebral hemorrhage. The Wilcoxon paired signed-rank test was used to qualitatively analyze the differences in the Arterial Transit Artifact (ATA) of the bilateral cerebral hemispheres. The mean gray value, the kurtosis and skewness of gray distribution curve of bilateral cerebral hemispheres on cerebral blood flow (CBF) images with post labeling delay (PLD) of 1.5 s and 2.5 s were quantitative calculated. The relationship between ASL and cerebrovascular event was determined using binary logistics regression analysis. Results: No significant difference was observed in ATA between bilateral hemispheres on CBF images with PLDs of 1.5 s and 2.5 s (P>0.05). On the CBF images with a PLD of 1.5 s, the mean gray value of the cerebral hemisphere on the lesion side (17.50±5.88) was markly lower than that on the non-lesion side (20.80±5.51) (P<0.001), the kurtosis and skewness of gray distribution were significantly different between bilateral cerebral hemispheres (P<0.05);On the CBF images with a PLD of 2.5 s, the mean gray value and the skewness of the gray distribution on the lesion side of the cerebral hemisphere were statistically different from those on the non-lesion side (P<0.05), while the difference in kurtosis was not statistically significant between bilateral cerebral hemispheres (P>0.05). Multivariate regression analysis showed that the reduction of gray value on the side of the lesion was independently associated to the occurrence of the cerebrovascular events (ORPLD1.5=0.192, 95%CI:0.047-0.783;ORPLD2.5=0.175, 95%CI:0.050-0.615). Conclusion: The decreased perfusion detected by ASL is independently associated with cerebrovascular events in patients with MMA.

How far is arterial spin labeling MRI from a clinical reality? Insights from arterial spin labeling comparative studies in Alzheimer's disease and other neurological disorders.

Cerebral ischemia is a leading cause of disability worldwide and no other effective therapy has been validated to date than intravenous thrombolysis. In this context, many preclinical models have been developed and recent advances in preclinical imaging represent promising tools. Thus, we proposed here to characterize invivo time profiles of cerebral blood flow, blood-brain barrier disruption and apoptosis following a transient middle cerebral artery occlusion in rats using SPECT/CT imaging. Rats underwent a 1-h middle cerebral artery occlusion followed by reperfusion. Cerebral blood flow, blood-brain barrier disruption and apoptosis were evaluated by SPECT/CT imaging using respectively (99m)Tc-HMPAO, (99m)Tc-DTPA and the experimental (99m)Tc-Annexin V-128, up to 14 days after middle cerebral artery occlusion. Histological evaluation of apoptosis has been performed using TUNEL method to validate the (99m)Tc-Annexin V-128 uptake. (99m)Tc-HMPAO cerebral blood flow evaluation showed hypoperfusion during occlusion, partially restored on days 4 and 7 and sustained up to 14 days after middle cerebral artery occlusion. (99m)Tc-DTPA SPECT/CT showed a blood-brain barrier disruption starting on day 1 post-middle cerebral artery occlusion, peaking on day 2, with barrier integrity totally restored on day 7. (99m)Tc-Annexin V-128 SPECT/CT imaging showed significant positive correlation with TUNEL immunohistochemistry and allowed ischemic-induced apoptosis to be detected from day 2 to day 7, peaking on day 3 after middle cerebral artery occlusion. Using SPECT/CT imaging, we showed that after transient middle cerebral artery occlusion in rat there was a sustained decrease in cerebral blood flow followed by blood-brain barrier disruption preceding meanwhile apoptosis. Rodent SPECT/CT imaging of cerebral blood flow, blood-brain barrier disruption and apoptosis appears to be an efficient tool for evaluating neuroprotective drugs and regenerative therapies against cerebral ischemia and time-windows for therapeutic intervention.

Recently, the technique of harmonic contrast imaging has been developed which exploits the nonlinear properties of ultrasound contrast agents by processing the second harmonic echo signal of the transmitted ultrasound pulse. The contrast agent employed is Levovist (Schering), which was released in Japan in 1999. The advantage of harmonic imaging is its selective imaging of differences between tissue and blood perfusion areas.The purpose of the present study was to investigate a method of detecting human brain perfusion by ultrasound with second harmonic signals and contrast agents in eight patients with brain tumors. We used pulse inversion harmonic imaging, which is the latest technique for visualizing ultrasound contrast agents, thereby allowing us to image brain perfusion, and well enhanced perfusion images were obtained in all cases.We performed analysis resulting in wash-in wash-out curves, and concluded that this method could be used for diagnosis of brain hemodynamics.

ObjectiveThis study was performed to evaluate the test–retest reliability of perfusion of the cortex and subcortical white matter on three-dimensional spiral fast spin echo pseudo-continuous arterial spin labeling (3D-ASL).MethodsEight healthy subjects underwent 3D-ASL and structural imaging at the same time each day for 1 week. ASL data acquisition was performed in the resting state and right finger-tapping state. Cerebral blood flow (CBF) images were calculated, and the CBF values of the precentral cortex (PCC) and precentral subcortical white matter (PCSWM) were automatically extracted based on the structural images and CBF images.ResultsIn the resting state, the intraclass correlation coefficient (ICC) of the bilateral PCC was 0.84 (left) and 0.81 (right) and that of the bilateral SCWM was 0.89 (left) and 0.85 (right). In the finger-tapping state, the ICC of the bilateral PCC was 0.91 (left) and 0.87 (right) and that of the bilateral PCSWM was 0.87 (left) and 0.92 (right). The CBF value of the left PCC and PCSWM was not significantly different between the resting state and finger-tapping state on two ASL scans.Conclusion3D-ASL provides reliable CBF measurement in the cortex and subcortical white matter in the resting or controlled state.

Color-coded perfusion maps can be calculated from ultrasound harmonic gray-scale imaging data after ultrasound contrast agent bolus injection to analyze brain tissue perfusion. First reports indicate that this method can display cerebral perfusion deficits in acute ischemic stroke. We performed a prospective patient study to evaluate this approach. Thirty consecutive patients suffering from acute middle cerebral artery infarction who presented to our department within 12 hours after symptom onset were investigated with ultrasound perfusion harmonic imaging (PHI) after Levovist bolus injection. Color-coded perfusion maps were calculated from the ultrasound data. In addition, the original gray-scale images were analyzed in cine mode. Findings were compared with those of cranial CT. All 30 patients suffered from acute ischemic stroke of the middle cerebral artery territory (median National Institutes of Health Stroke Scale score, 16 points). Twenty-three of the 30 patients (76.7%) had sufficient PHI insonation conditions. In 19 of these 23 patients (82.6%), a marked deficit in contrast enhancement could be visualized by initial PHI with the color-coded parameter images and cine-mode images. In 17 of the 23 (73.9%), the perfusion deficit was found on the parameter images. The area of hypoperfusion in the initial PHI investigation corresponded to the definite area of infarction in follow-up cranial CT. In 3 of 23 patients (13.0%), a perfusion deficit could be demonstrated in PHI, although the supplying artery was found patent by transcranial color-coded duplex sonography. With PHI, it is possible to display cerebral perfusion deficits in acute ischemic stroke. PHI yields additional information on the perfusion state of the human brain compared with extracranial and transcranial color-coded duplex sonography.

New concept in echocardiography: harmonic imaging of tissue without use of contrast agent

This presentation will introduce three techniques that we have recently developed for microscopic imaging of cerebral blood flow (CBF) in both large vessels and capillaries. The techniques are based on optical coherence tomography (OCT). First, we integrated OCT with dynamic light scattering analysis, enabling us to measure both axial and transverse velocities at every voxel of OCT. Meanwhile, as red blood cells (RBCs) flow one by one in capillaries, the traditional decorrelation-based methods may not be suitable for quantifying the RBC flow properties of capillaries. Here, we developed another technique based on the finding that individual RBC passage can be captured in the OCT intensity signal time course. This technique enabled volumetric estimation of capillary RBC speed, flux, and density. Finally, we developed the third technique for rapid volumetric imaging of RBC flux over a capillary network, with a high temporal resolution of ~1 s that is essential for tracing fast hemodynamic responses.

Chronic imaging of cerebral blood flow (CBF) is an important tool for investigating vascular remodeling after injury such as stroke. Although techniques such as Laser Speckle Contrast Imaging (LSCI) have emerged as valuable tools for imaging CBF in acute experiments, their utility for chronic measurements or cross-animal comparisons has been limited. Recently, an extension to LSCI called Multi-Exposure Speckle Imaging (MESI) was introduced that increases the quantitative accuracy of CBF images. In this paper, we show that estimates of chronic blood flow are better with MESI than with traditional LSCI. We evaluate the accuracy of the MESI flow estimates using red blood cell (RBC) photographic tracking as an absolute flow calibration in mice over several days. The flow measures computed using the MESI and LSCI techniques were found to be on average 10% and 24% deviant (n=9 mice), respectively, compared with RBC velocity changes. We also map CBF dynamics after photo-thrombosis of selected cortical microvasculature. Correlations of flow dynamics with RBC tracking were closer with MESI (r=0.88) than with LSCI (r=0.65) up to 2 weeks from baseline. With the increased quantitative accuracy, MESI can provide a platform for studying the efficacy of stroke therapies aimed at flow restoration.

Noninvasive noncontact speckle contrast diffuse correlation tomography of cerebral blood flow in rats

Sickle cell disease is characterized by chronic hemolytic anemia and vascular inflammation, which can diminish the vasodilatory capacity of the small resistance arteries, making them less adept at regulating cerebral blood flow. Autoregulation maintains adequate oxygen delivery, but when vasodilation is maximized, the low arterial oxygen content can lead to ischemia and silent cerebral infarcts. We used magnetic resonance imaging of cerebral blood flow to quantify whole-brain cerebrovascular reserve in 36 adult patients with sickle cell disease (mean age, 31.9±11.3 years) and 11 healthy controls (mean age, 37.4±15.4 years), and we used high-resolution 3D FLAIR magnetic resonance imaging to determine the prevalence of silent cerebral infarcts. Cerebrovascular reserve was calculated as the percentage change in cerebral blood flow after a hemodynamic challenge with acetazolamide. Co-registered lesion maps were used to demonstrate prevalent locations for silent cerebral infarcts. Cerebral blood flow was elevated in patients with sickle cell disease compared to controls (median [interquartile range]: 82.8 [20.1] vs. 51.3 [4.8] mL/100g/min, P<0.001). Cerebral blood flow was inversely associated with age, hemoglobin, and fetal hemoglobin, and correlated positively with bilirubin, and LDH, indicating that cerebral blood flow may reflect surrogates of hemolytic rate. Cerebrovascular reserve in sickle cell disease was decreased by half compared to controls (34.1 [33.4] vs. 69.5 [32.4] %, P<0.001) and was associated with hemoglobin and erythrocyte count indicating anemia-induced hemodynamic adaptations. In total, 29/36 patients (81%) and 5/11 controls (45%) had silent cerebral infarcts (median volume of 0.34 vs. 0.02 mL, P=0.03). Lesions were preferentially located in the borderzone. In conclusion, patients with sickle cell disease have a globally reduced cerebrovascular reserve as determined by arterial spin labeling with acetazolamide and reflects anemia–induced impaired vascular function in sickle cell disease. This study was registered at clinicaltrials.gov identifier 02824406.

Extremely preterm infants’ hemodynamic instability places them at high risk of brain injury. Currently there is no reliable bedside method to continuously monitor cerebral hemodynamics in the neonatal intensive care unit (NICU). This paper reports a feasibility study to adapt and test an innovative speckle contrast diffuse correlation tomography (scDCT) device for noncontact, high-density, 3D imaging of cerebral blood flow (CBF) in preterm infants. The scDCT scans a focused point near-infrared illumination to multiple source positions for deep tissue penetration, and controls an electron multiplying charge-coupled-device camera with thousands of pixels to achieve a high-density sampling. The optimized scDCT for use in preterm infants was first evaluated against an established diffuse correlation spectroscopy in an infant-head-simulating phantom with known properties. The observed significant correlation between the two measurements verified the capability of scDCT for transcranial brain imaging. The insignificant influence of transparent incubator wall on scDCT measurements was then confirmed by comparing adult forearm blood flow responses to artery cuff occlusions measured inside and outside the incubator. Finally, the scDCT device was moved to the NICU to image CBF variations in two preterm infants. Infant #1 with no major organ deficits showed little CBF fluctuation over the first 3 weeks of life. Infant #2 showed a significant CBF increase after the 2 h pharmacotherapy for patent ductus arteriosus closure. While these CBF variations meet physiological expectations, the fact that no significant changes are noted with peripheral monitoring of blood oxygen saturation suggests necessity of direct cerebral monitoring. This feasibility study with timely technology development is an important and necessary step towards larger clinical studies with more subjects to further validate it for continuous monitoring and instant management of cerebral pathologies and interventions in the NICU.

Tomographic images of cerebral blood flow (CBF) and oxygen extraction fraction (OEF) using the 15O continuous inhalation technique, and positron emission tomography, were obtained from a patient with cerebral ischemia distal to an occluded left internal carotid artery. There was a focal mismatch between CBF and oxygen metabolism in the brain supplied by the middle cerebral artery where CBF was decreased and OEF increased ("misery-perfusion syndrome" as opposed to "luxury-perfusion syndrome"). These abnormalities were most marked in the parieto-occipital watershed area. After left superficial temporal to middle cerebral artery anastomosis, the clinical attacks ceased and a repeat study did not demonstrate the previous CBF and OEF abnormalities. This suggests that this pattern of abnormalities indicates potential viable tissue. The concept of "misery-perfusion" may be of some importance in the pathophysiological mechanisms of hemodynamic cerebral ischemia and serve as a rational basis for revascularization procedures.

Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex