Quantification of Cerebral Perfusion With “Real-Time” Contrast-Enhanced Ultrasound

Rim, Se Joong; Leong‐Poi, Howard; Lindner, Jonathan R.; Couture, Daniel E.; Ellegala, Dilantha B.; Mason, Holland; Durieux, Marcel E.; Kassel, Neal F.; Kaul, Sanjiv

doi:10.1161/hc4601.099400

Cited by 102 publications

(58 citation statements)

References 32 publications

(22 reference statements)

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“…CEU has been used to measure microvascular perfusion in the myocardium (32) and has recently been applied to brain (24) and renal perfusion (17). Most recently, we (12,30) have applied this technique to measure the effect of insulin on microvascular perfusion in skeletal muscle.…”

Section: Experimental Protocolsmentioning

confidence: 99%

Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin

Vincent¹,

Barrett²,

Lindner³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

272

312

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. Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin. Am J Physiol Endocrinol Metab 285: E123-E129, 2003; 10.1152/ajpendo.00021.2003.-We examined the effects of inhibiting nitric oxide synthase with N -nitro-L-arginine-methyl ester (L-NAME) on total hindlimb blood flow, muscle microvascular recruitment, and hindlimb glucose uptake during euglycemic hyperinsulinemia in vivo in the rat. We used two independent methods to measure microvascular perfusion. In one group of animals, microvascular recruitment was measured using the metabolism of exogenously infused 1-methylxanthine (1-MX), and in a second group contrast-enhanced ultrasound (CEU) was used. Limb glucose uptake was measured by arterial-venous concentration differences after 2 h of insulin infusion. Saline alone did not alter femoral artery flow, glucose uptake, or 1-MX metabolism. Insulin (10 mU ⅐ min Ϫ1 ⅐ kg Ϫ1 ) significantly increased hindlimb total blood flow (0.69 Ϯ 0.02 to 1.22 Ϯ 0.11 ml/min, P Ͻ 0.05), glucose uptake (0.27 Ϯ 0.05 to 0.95 Ϯ 0.08 mol/min, P Ͻ 0.05), 1-MX uptake (5.0 Ϯ 0.5 to 8.5 Ϯ 1.0 nmol/min, P Ͻ 0.05), and skeletal muscle microvascular volume measured by CEU (10.0 Ϯ 1.6 to 15.0 Ϯ 1.2 video intensity units, P Ͻ 0.05). Addition of L-NAME to insulin completely blocked the effect of insulin on both total limb flow and microvascular recruitment (measured using either 1-MX or CEU) and blunted glucose uptake by 40% (P Ͻ 0.05). We conclude that insulin specifically recruits flow to the microvasculture in skeletal muscle via a nitric oxide-dependent pathway and that this may be important to insulin's overall action to regulate glucose disposal. capillary recruitment; nitric oxide; nitric oxide synthase; muscle blood flow THERE IS ABUNDANT EVIDENCE that insulin augments total limb blood flow in humans (2, 29, 33) and experimental animals (20, 22) in a time-and dose-dependent fashion. It has been suggested that this action of insulin could, by facilitating the delivery of glucose and itself to muscle, contribute to insulin's overall action on glucose disposal (3), although this remains controversial (33).Substantial evidence suggests that nitric oxide (NO) is involved in insulin's action to increase limb blood flow in humans (5,8,25,26,29). NO in muscle is produced by nitric oxide synthase (NOS), located in both vascular endothelium (28) and myocytes (16). Inhibition of NO production by N -mono-methyl-L-arginine (L-NMMA) can fully abolish the effect of insulin to increase limb total blood flow in humans (4,5,26,29). In one study, this agent partially blocked (ϳ25%) insulin-mediated glucose uptake as well (5). Baron et al. (6) have also reported that, in the rat, L-NMMA increases mean arterial pressure and reduces whole body glucose infusion rate in a dose-dependent fashion during a euglycemic insulin clamp (12 mU⅐min Ϫ1 ⅐kg Ϫ1). Using intravital microscopy, Chen and Messina (8) demonstrated that insulin induces vasodilation of firstorder arterioles in rat cremaster and that the addition...

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Section: Experimental Protocolsmentioning

confidence: 99%

Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin

Vincent¹,

Barrett²,

Lindner³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

272

312

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“…More recently, it was shown that the resulting parameters also semiquantitatively describe perfusion in the brain of the dog 11 and can be used to calculate CBF values in dogs with craniotomies by means of radiolabeled microspheres. 12 The first results of a study with volunteers indicate that the method can be performed effectively in humans as well. 13 In 12 probands, within the ipsilateral thalamus it was possible to display a homogeneous visualization of perfusion according to the parameters describing blood flow and refill velocity.…”

Section: Discussionmentioning

confidence: 99%

Re: Telephone Intervention With Family Caregivers of Stroke Survivors After Rehabilitation

Friedman

2003

Stroke

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Background and Purpose-Established methods of ultrasonic perfusion imaging using a bolus application of echo contrast agent provide only qualitative data because of various physical phenomena. This study was intended to investigate whether a new ultrasound perfusion imaging method termed contrast burst depletion imaging (CODIM) may provide semiquantitative measures of parenchymal perfusion independent of examination depth and acoustic energy distribution. Methods-In a system with a constant concentration of contrast agent, analyzing the decrease in image intensity that occurs with microbubble-destructive imaging modes yields parameters that are considered to correlate with tissue perfusion. This method was first evaluated with a perfusion model that showed that the main resulting parameter "perfusion coefficient" (PC) is a monotonic nonlinear function of flow velocity. Seventeen human volunteers were then scanned according to this method with the use of 2 different contrast agents. Results were correlated with those from perfusion-weighted MRI examinations. Results-The PC did not show significant differences in gray matter areas (ranging from 1.466ϫ10Ϫ2 s Ϫ1 to 1.641ϫ10

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“…In the original paper of Wei et al (1998), the b parameter was described to be directly related to blood flow velocity, and the plateau of acoustic intensity A related to blood volume. The product of both (A Â b) correlated with the blood flow as measured by radiolabeled microspheres (Wei et al, 1998;Rim et al, 2001). …”

Section: Technical Principles Of Microbubble Refill Kineticsmentioning

confidence: 96%

Real-Time Ultrasound Brain Perfusion Imaging with Analysis of Microbubble Replenishment in Acute MCA Stroke

Kern

Diels

Pettenpohl

et al. 2011

J Cereb Blood Flow Metab

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Real-time ultrasound perfusion imaging (rt-UPI) allows visualization of microbubbles flowing through the cerebral microvasculature. We hypothesized that analysis of microbubble tissue replenishment would enable for characterization of perfusion deficits in acute middle cerebral artery (MCA) territory stroke. Twenty-three patients (mean age 70.2±13.2 years, 9 weeks) were included. Sequential images of bubble replenishment were acquired by transcranial rt-UPI at low mechanical index immediately after microbubble destruction. Different parameters were calculated from regions of interest (ROIs): real-time time to peak (rt-TTP), rise rate (b), and plateau (A) of acoustic intensity, and A¾b was used as an index of blood flow. Results were compared with diffusion-weighted and perfusion magnetic resonance imaging. Parameters of rt-UPI had lower values in ROIs of ischemic as compared with normal tissue (b = 0.58 ± 0.40 versus 1.25 ± 0.83; P = 0.001; A = 1.44 ± 1.75 versus 2.63 ± 2.31; P = 0.05; A¾b = 1.14 ± 2.25 versus 2.98 ± 2.70; P = 0.01). Real-time time to peak was delayed in ischemic tissue (11.43 ± 2.67 versus 8.88 ± 1.66 seconds; P < 0.001). From the analysis of receiver operating characteristic curves, b and A¾b had the largest areas under the curve with optimal cutoff values of b < 0.76 and A¾b < 1.91. We conclude that rt-UPI with analysis of microbubble replenishment correctly identifies ischemic brain tissue in acute MCA stroke.

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Quantification of Cerebral Perfusion With “Real-Time” Contrast-Enhanced Ultrasound

Cited by 102 publications

References 32 publications

Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin

Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin

Re: Telephone Intervention With Family Caregivers of Stroke Survivors After Rehabilitation

Real-Time Ultrasound Brain Perfusion Imaging with Analysis of Microbubble Replenishment in Acute MCA Stroke

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