Non-Invasive Assessment of Dynamic Cerebral Blood Flow Using Near-Field Coupling and Synchronized Electrocardiography.

On the theory of the indicator-dilution method for measurement of blood flow and volume.

Upon ascent to high altitude, cerebral blood flow (CBF) rises substantially before returning to sea-level values. The underlying mechanisms for these changes are unclear. We examined three hypotheses: (1) the balance of arterial blood gases upon arrival at and across 2 weeks of living at 5050 m will closely relate to changes in CBF; (2) CBF reactivity to steady-state changes in CO2 will be reduced following this 2 week acclimatisation period, and (3) reductions in CBF reactivity to CO2 will be reflected in an augmented ventilatory sensitivity to CO2. We measured arterial blood gases, middle cerebral artery blood flow velocity (MCAv, index of CBF) and ventilation () at rest and during steady-state hyperoxic hypercapnia (7% CO2) and voluntary hyperventilation (hypocapnia) at sea level and then again following 2–4, 7–9 and 12–15 days of living at 5050 m. Upon arrival at high altitude, resting MCAv was elevated (up 31 ± 31%; P < 0.01; vs. sea level), but returned to sea-level values within 7–9 days. Elevations in MCAv were strongly correlated (R2= 0.40) with the change in ratio (i.e. the collective tendency of arterial blood gases to cause CBF vasodilatation or constriction). Upon initial arrival and after 2 weeks at high altitude, cerebrovascular reactivity to hypercapnia was reduced (P < 0.05), whereas hypocapnic reactivity was enhanced (P < 0.05 vs. sea level). Ventilatory response to hypercapnia was elevated at days 2–4 (P < 0.05 vs. sea level, 4.01 ± 2.98 vs. 2.09 ± 1.32 l min−1 mmHg−1). These findings indicate that: (1) the balance of arterial blood gases accounts for a large part of the observed variability (∼40%) leading to changes in CBF at high altitude; (2) cerebrovascular reactivity to hypercapnia and hypocapnia is differentially affected by high-altitude exposure and remains distorted during partial acclimatisation, and (3) alterations in cerebrovascular reactivity to CO2 may also affect ventilatory sensitivity.

PurposeA recently developed technique which reconstructs quantitative images from original projection data acquired using existing single-photon emission computed tomography (SPECT) devices enabled quantitative assessment of cerebral blood flow (CBF) at rest and after acetazolamide challenge. This study was intended to generate a normal database and to investigate its inter-institutional consistency.Methods The three institutions carried out a series of SPECT scanning on 32 healthy volunteers, following a recently proposed method that involved dual administration of 123I-iodoamphetamine during a single SPECT scan. Intra-institute and inter-institutional variations of regional CBF values were evaluated both at rest and after acetazolamide challenge. Functional images were pooled for both rest and acetazolamide CBF, and inter-institutional difference was evaluated among these images using two independent software programs.ResultsQuantitative assessment of CBF images at rest and after acetazolamide was successfully achieved with the given protocol in all institutions. Intra-institutional variation of CBF values at rest and after acetazolamide was consistent with previously reported values. Quantitative CBF values showed no significant difference among institutions in all regions, except for a posterior cerebral artery region after acetazolamide challenge in one institution which employed SPECT device with lowest spatial resolution. Pooled CBF images at rest and after acetazolamide generated using two software programs showed no institutional differences after equalization of the spatial resolution.Conclusions SPECT can provide reproducible images from projection data acquired using different SPECT devices. A common database acquired at different institutions may be shared among institutions, if images are reconstructed using a quantitative reconstruction program, and acquired by following a standardized protocol.

To determine the short-term effects of antihypertensive therapy on cerebral blood flow (CBF). Prospective, observational study. A university-affiliated teaching hospital. Twenty-four patients (age range 53-85 yrs) with chronic hypertension, nine of whom had carotid artery occlusive disease (CAOD). The CBF (xenon-133 inhalation technique) and blood pressure were measured before and at 60 minutes after administration of antihypertensive therapy. Age was inversely related to the change in CBF in patients with CAOD (p < 0.01). In all patients, the change in CBF after taking antihypertensive drugs was significantly inversely associated with baseline CBF (p < 0.01). Changes in regional CBF, measured by asymmetry scores, were significantly greater in patients with CAOD than in those without CAOD (p < 0.05). Elderly patients with occlusive extracranial cerebrovascular disease are at risk of drug-induced changes in both mean and regional CBF, and may benefit from a CBF assessment before being prescribed antihypertensive therapy.

Oligodendrogliomas, molecularly defined by the presence of both IDH mutation and 1p/19q codeletion, are more treatment responsive than other gliomas, and due to short capillary segments, demonstrate elevated CBF regardless of grade or contrast enhancement. Arterial Spin Labeling (ASL) allows noninvasive perfusion imaging assessment of cerebral blood flow (CBF) without contrast administration. Changes in CBF are recognized in association with malignant transformation of gliomas however in the setting of treatment, CBF has only been studied to assist in differentiating radiation treatment effect from progressive glioma. This single center retrospective study was undertaken to evaluate if CBF, measured by ASL, might normalize following treatment of recurrent oligodendrogliomas. Clinical database query identified 151 patients with molecularly confirmed oligodendroglioma, 34 of which had available ASL imaging. Expert reader review of all available MRI sequences, blinded to treatment timeline, were performed by two independent radiologists at a PACS station. There were 6 radiographic recurrences identified and in 5/6 CBF was the first radiographic change. Contrast enhancement did not develop for 1.5-12 months after change in CBF for 4/5 recurrences. ASL imaging before and after non-surgical therapy for recurrent disease was available for 4 patients. Two patients were treated with lomustine, one with bevacizumab and one with proton re-radiation. By the second MRI following treatment initiation, all patients had normalization of CBF. At the first post treatment MRI, 3/4 of patients demonstrated normalization of CBF while only 2/4 demonstrated normalization of dynamic susceptibility contrast-derived cerebral blood volume. During the subsequent 6 months, FLAIR hyperintensities remained stable in all patients. This work supports further study if normalization of ASL-derived CBF may be an early radiographic biomarker for response to treatment, especially in non or minimally enhancing recurrent gliomas.

Currently, reliable low-cost and noninvasive techniques to assess cerebral perfusion in the operating room are not available. The authors report on their first clinical experience with laser speckle contrast analysis (LASCA) as a complementary imaging tool for the noninvasive and dynamic assessment of cerebral blood flow (CBF) during neurovascular surgery. The purpose of this preliminary study was to address the general feasibility of LASCA in terms of handling and image quality and to provide an example of its clinical implications. Laser speckle contrast analysis was performed in patients undergoing cerebral revascularization procedures for the treatment of hemodynamic compromise and complex aneurysms. The portable LASCA device was centered over the surgical field, and continuous 5-minute recordings of relative CBF were obtained. In the case of flow augmentation for hemodynamic compromise, CBF monitoring was performed before and after completion of the anastomosis. In the case of flow replacement for parent artery sacrifice, CBF monitoring was performed during consecutive 30-second test occlusions of the radial artery graft after proximal internal carotid artery sacrifice and the subsequent initiation of blood flow through the bypass. In all cases, the authors achieved good visualization of relative CBF in addition to flow imaging in both the bypass graft and the cortical vasculature. During a sudden CBF decrease after test occlusion of the radial artery graft and subsequent flow initiation through the bypass, LASCA allowed immediate visualization and measurement of relative CBF in excellent spatiotemporal resolution. In this study LASCA offered noninvasive and rapid intraoperative assessment of relative CBF, which can be used for optimizing neurovascular procedures.

Transcranial Doppler ultrasonography has been reported to reflect changes in cerebral blood flow (CBF) with the use of radioactive tracer techniques, which are weighted to measure primarily cortical structures. We tested the hypothesis that changes in transcranial Doppler ultrasonography would reflect changes in CBF in the middle cerebral artery vascular territory with the use of stable xenon-enhanced CT to assess CBF during carotid occlusion. Thirty-one conscious patients underwent balloon test occlusion of the internal carotid artery and transcranial Doppler ultrasonography and xenon-enhanced CT assessment of blood flow velocity and CBF, respectively, of the middle cerebral artery and its distribution during balloon test occlusion. A significant correlation was seen between the change in CBF and the change in blood flow velocity for both brain levels at which CBF was determined (P < .0001). The average change in blood flow velocity was -13.4%, and the change in CBF was -15.1% and -17.7% at the two anatomic levels examined. The data indicate that changes in blood flow velocity generally reflect changes in CBF throughout the middle cerebral artery vascular territory with abrupt occlusion of the internal carotid artery in unanesthetized humans.

Cerebral blood flow and oxygen consumption in man.

Measurement of cerebral blood flow with dynamic susceptibility contrast MRI and comparison with O-15 positron emission tomography

170 patients were divided into two groups: Group 1- diffuse TBI (75 patients); and Group 2- TBI with IH (95 patients: 18 epidural, 65 subdural and 12 multiple). Perfusion computed tomography (PCT) for assessment of volumetric cerebral blood flow (CBF) was done 2-15days after admission to hospital. Simultaneous assessment of cerebral blood flow velocity (CBFV) in both middle cerebral arteries was done by transcranial Doppler. In patients with diffuse TBI, CBF had statistically valid correlations with CBFV (r=0.28, p=0.0149 on the left side; r=0.382, p=0.00075 on the right side). In patients with TBI and IH, the analysis did not reveal any reliable correlations between the CBFV and CBF velocity in the temporal lobes, either on the side of the removed IH or on the opposite side. The greatest linear correlation was noted in patients with diffuse TBI without the development of a coarse shift of the midline structures and dislocation syndrome. This correlation decreases with the increase in injury severity and development of secondary complications in the acute period, which probably reflects impairment of the coupling of oxygen consumption by brain tissue and cerebral microcirculation.

Cortical spreading depolarizations (CSDs) are self-propagating waves of transient loss of neuronal transmembrane ion gradients, followed by prolonged suppression of neuronal activity (spreading depression). CSDs emerge spontaneously in animal models of traumatic brain injury,1 subarachnoid hemorrhage,2 and in focal ischemia3 where they are associated with infarct growth.4 In humans, CSDs have been demonstrated in traumatic brain injury,5 subarachnoid hemorrhage,6,7 and malignant hemispheric stroke,8 and they are believed to be the brain mechanism underlying migraine aura.9 CSDs are associated with dramatic changes in cerebral blood flow (CBF). During the depolarization phase of CSDs induced in healthy and well-perfused brain tissue in animal models, an early hyperemic response is observed, typically followed by prolonged oligemia after the neuronal repolarization. Despite the initial CBF increase, tissue hypoxia may develop in more distant territories of capillary supply.10,11 Similar CBF changes have been observed in patients with migraine aura.12–14 In the injured brain, CSDs can be accompanied by severe initial CBF reduction instead of a CBF increase during the depolarization phase, termed spreading ischemia.15 When this inverse hemodynamic response is observed, the energy-dependent recovery from CSD is delayed in a characteristic fashion, indicating a severe mismatch between oxygen supply and demand2 and a high risk of tissue damage.16 In rat and cat models of focal ischemia, CSD-related CBF transients range from monophasic, positive CBF responses in peri-ischemic tissue, over biphasic transients in mildly ischemic tissue, to negative CBF transients in more severe ischemia.17–19 During CSD in animal models, capillary flow patterns become severely disturbed.10,20,21 The passage of a CSD causes erythrocytes in some capillaries to reduce their speed, whereas other capillaries reveal 4-fold increases in flow or higher. …

The aim was to validate the MRI assessment of regional cerebral blood flow. Measurements were performed on a 1.5 T imaging system using a fast T2*-weighted gradient-echo sequence. After intravenous injection of gadolinium-DTPA 30 images were acquired in the same slice position during 84 seconds. In 12 volunteers we observed a symmetrical cortical decrease of signal intensity during the passage of the contrast medium. In 9/23 patients with impairment of cerebral blood flow a circumscribed area of reduced signal intensity decrease (hypoperfusion) was found. In 4/23 patients the decrease of signal intensity was more pronounced than in normals (hyperfusion). In 9/23 patients signal intensity changes were normal. HMPAO-SPECT confirmed successful MRI assessment of cerebral blood flow in 22/23 patients.

Toward Improved Neurodevelopmental Outcomes: The Role of Transfontanel Ultrasound Assessment of Cerebral Blood Flow in Infants Undergoing Cardiac Surgery

The peak amplitude of pulsatile cerebral electrical impedance (delta Zp) was compared with simultaneous 133xenon clearance estimations of cerebral blood flow (CBF infinity) on 28 occasions in nine infants receiving assisted ventilation who had changes in PaCO2 and thereby presumably in cerebral blood flow. Percentage changes from one measurement to the next in each infant were compared. Using linear regression the relationship was delta Zp = 0.5 CBF infinity-1.5 with r = 0.67. The 95% confidence interval for the regression coefficient was 0.2-0.8 and the mean residual was 28%. Changes in cerebral blood flow in these clinical conditions were similarly detected by the two methods but delta Zp underestimated the magnitude of the change in comparison with CBF infinity and its accuracy was insufficient to allow conclusions about the magnitude of small changes in cerebral blood flow in individual infants.

BackgroundAssessment of cerebral blood flow (CBF) by SPECT could be important in the management of patients with severe traumatic brain injury (TBI) because changes in regional CBF can affect outcome by promoting edema formation and intracranial pressure elevation (with cerebral hyperemia), or by causing secondary ischemic injury including post-traumatic stroke. The purpose of this study was to establish an improved method for evaluating regional CBF changes after TBI in piglets.MethodsThe focal effects of moderate traumatic brain injury (TBI) on cerebral blood flow (CBF) by SPECT cerebral blood perfusion (CBP) imaging in an animal model were investigated by parallelized statistical techniques. Regional CBF was measured by radioactive microspheres and by SPECT 2 hours after injury in sham-operated piglets versus those receiving severe TBI by fluid-percussion injury to the left parietal lobe. Qualitative SPECT CBP accuracy was assessed against reference radioactive microsphere regional CBF measurements by map reconstruction, registration and smoothing. Cerebral hypoperfusion in the test group was identified at the voxel level using statistical parametric mapping (SPM).ResultsA significant area of hypoperfusion (P < 0.01) was found as a response to the TBI. Statistical mapping of the reference microsphere CBF data confirms a focal decrease found with SPECT and SPM.ConclusionThe suitability of SPM for application to the experimental model and ability to provide insight into CBF changes in response to traumatic injury was validated by the SPECT SPM result of a decrease in CBP at the left parietal region injury area of the test group. Further study and correlation of this characteristic lesion with long-term outcomes and auxiliary diagnostic modalities is critical to developing more effective critical care treatment guidelines and automated medical imaging processing techniques.