Current concepts in assessment of microvascular endothelial function using laser Doppler imaging and iontophoresis.

Effective evaluation of endothelial function is a powerful tool for determining patients at risk of development and progression of cardiovascular disease. As an alternative to invasive tests of endothelial function, several noninvasive methods have been developed, including the use of laser Doppler flowmetry/imaging to measure cutaneous perfusion accompanied by iontophoresis of acetylcholine and sodium nitroprusside. It is clear from previous studies that this technique provides an easy, validated, and reproducible method for investigators to assess and monitor endothelial function in patients with a variety of pathologic conditions, but it may also be used to examine disease progression over time and responsiveness to treatment, thereby facilitating clinical trials. However, a standardization of protocols would help reduce the apparent controversy seen in the literature. With its increasing use by other groups, it is anticipated that further published studies will help to provide a better understanding of the development and progression of cardiovascular disease.

Absence of glutathione peroxidase-1 exacerbates cerebral ischemia-reperfusion injury by reducing post-ischemic microvascular perfusion.

Mice deficient in the anti-oxidant enzyme glutathione peroxidase-1 (Gpx1) have a greater susceptibility to cerebral injury following a localized ischemic event. Much of the response to ischemia-reperfusion is caused by aberrant responses within the microvasculature, including inflammation, diminished endothelial barrier function (increased vascular permeability), endothelial activation, and reduced microvascular perfusion. However, the role of Gpx1 in regulating these responses has not been investigated. Wild-type and Gpx1-/- mice underwent focal cerebral ischemia via mid-cerebral artery occlusion followed by measurement of cerebral perfusion via laser Doppler and intravital microscopy. Post-ischemic brains in wild-type mice displayed significant deficit in microvascular perfusion. However, in Gpx1-/- mice, the deficit in cerebral blood flow was significantly greater than that in wild-type mice, and this was associated with significant increase in infarct size and increased vascular permeability. Ischemia-reperfusion also resulted in expression of matrix metalloproteinase-9 (MMP-9) in endothelial cells. The absence of Gpx1 was associated with marked increase in pro-MMP-9 expression as well as potentiated MMP-9 activity. Pre-treatment of Gpx1-/- mice with the anti-oxidant ebselen restored microvascular perfusion, limited the induction and activation of MMP-9, and attenuated the increases in infarct size and vascular permeability. These findings demonstrate that the anti-oxidant function of Gpx1 plays a critical role in protecting the cerebral microvasculature against ischemia-reperfusion injury by preserving microvascular perfusion and inhibiting MMP-9 expression.

Realtime photoacoustic microscopy in vivo with a 30-MHz ultrasound array transducer.

We present a novel high-frequency photoacoustic microscopy system capable of imaging the microvasculature of living subjects in realtime to depths of a few mm. The system consists of a high-repetition-rate Q-switched pump laser, a tunable dye laser, a 30-MHz linear ultrasound array transducer, a multichannel high-frequency data acquisition system, and a shared-RAM multi-core-processor computer. Data acquisition, beamforming, scan conversion, and display are implemented in realtime at 50 frames per second. Clearly resolvable images of 6-microm-diameter carbon fibers are experimentally demonstrated at 80 microm separation distances. Realtime imaging performance is demonstrated on phantoms and in vivo with absorbing structures identified to depths of 2.5-3 mm. This work represents the first high-frequency realtime photoacoustic imaging system to our knowledge.

Changes of cerebral blood flow during the secondary expansion of a cortical contusion assessed by 14C-iodoantipyrine autoradiography in mice using a non-invasive protocol.

Although changes of cerebral blood flow (CBF) in and around traumatic contusions are well documented, the role of CBF for the delayed death of neuronal cells in the traumatic penumbra ultimately resulting in secondary contusion expansion remains unclear. The aim of the current study was therefore to investigate the relationship between changes of CBF and progressive peri-contusional cell death following traumatic brain injury (TBI). CBF and contusion size were measured in C57Bl6 mice under continuous on-line monitoring of (ETp)CO2 before, and at 15 min and 24 h following controlled cortical impact by 14C-iodoantipyrine autoradiography (IAP-AR; n = 5-6 per group) and by Nissl staining, respectively. Contused and ischemic (CBF < 10%) tissue volumes were calculated and compared over time. Cortical CBF in not injured mice varied between 69 and 93 mL/100mg/min depending on the anatomical location. Fifteen minutes after trauma, CBF decreased in the whole brain by approximately 50% (39 +/- 18 mL/100mg/min; p < 0.05), except in contused tissue where it fell by more than 90% (3 +/- 2 mL/100mg/min; p < 0.001). Within 24 h after TBI, CBF recovered to normal values in all brain areas except the contusion where it remained reduced by more than 90% (p < 0.001). Contusion volume expanded from 24.9 to 35.5 mm3 (p < 0.01) from 15 min to 24 h after trauma (+43%), whereas the area of severe ischemia (CBF < 10%) showed only a minimal (+13%) and not significant increase (22.3 to 25.1 mm3). The current data therefore suggest that the delayed secondary expansion of a cortical contusion following traumatic brain injury may not be caused by a reduction of CBF alone.

Cerebral small vessel disease and C-reactive protein: results of a cross-sectional study in community-based Japanese elderly.

BACKGROUND AND PURPOSE: Inflammatory processes are involved in the pathogenesis of atherosclerosis. Inflammation has been known as a risk factor for coronary heart disease, whereas inflammation as a risk for cerebrovascular disease is less well established. Whether inflammatory processes, excluded from their involvement in large-vessel disease, are implicated in the pathogenesis of cerebral small vessel disease remains unclear. We assessed whether higher C-reactive protein (CRP) levels were associated with an increased number of lacunar infarcts or severity of white matter lesions. METHODS AND RESULTS: In a community-based group of Japanese elderly (n=689), CRP concentrations were measured using a highly sensitive assay. All participants underwent magnetic resonance imaging (MRI), and cerebral small vessel disease-related lesions (lacunar infarcts and white matter hyperintensity) were subsequently evaluated. Furthermore, carotid atherosclerosis was also assessed with ultrasonography. As the grades of white matter hyperintensity and the numbers of lacunes were considered small vessel disease-related lesions, we evaluated the relationships between CRP levels and small vessel disease-related brain lesions. Interestingly, the median CRP concentration of our participants was remarkably lower, being approximately one third or one quarter of the value of Western populations. Subjects with higher CRP levels tended to have more small vessel disease-related lesions; however, these associations were not seen after adjustment for cardiovascular risk factors and carotid atherosclerosis. CONCLUSIONS: The relationship between CRP levels and small vessel disease-related lesions was not apparent in the community-based Japanese elderly. The impact of inflammation in the pathogenesis of small vessel disease-related brain lesions seems to be weak among the Japanese elderly.

Synchrotron radiation coronary microangiography for morphometric and physiological evaluation of myocardial neovascularization induced by endothelial progenitor cell transplantation.

BACKGROUND: Therapeutic effect of stem cell transplantation (SCTx) for myocardial neovascularization has been evaluated by histological capillary density in small animals. However, it has been technically difficult to obtain imaging evidence of collateral formation by conventional angiography. METHODS AND RESULTS: Peripheral blood CD34+ and CD34- cells were isolated from patients with critical limb ischemia. PBS, CD34- cells, or CD34+ cells were intramyocardially transplanted after ligating LAD of nude rats. Coronary angiography of ex vivo beating hearts 5 and 28 days after the treatment was performed using the third generation synchrotron radiation microangiography (SRM), which has potential to visualize vessels as small as 20 microm in diameter. The SRM was performed pre and post sodium nitroprusside (SNP) to examine vascular physiology at each time point. Diameter of most collateral vessels was 20 to 120 microm, apparently invisible size in conventional angiography. Rentrop scores at day 28 pre and post SNP were significantly greater in CD34+ cell group than other groups (P<0.01). To quantify the extent of collateral formation, angiographic microvessel density (AMVD) in the occluded LAD area was analyzed. AMVD on day 28 post SNP, not pre SNP, was significantly augmented in CD34+ cell group than other groups (P<0.05). AMVD post SNP closely correlated with histological capillary density (R=0.82, P<0.0001). CONCLUSIONS: The SRM, capable of visualizing microvessels, may be useful for morphometric and physiological evaluation of coronary collateral formation by SCTx. The novel imaging system may be an essential tool in future preclinical/translational research of stem cell biology.

Total blush score: a new index for the assessment of microvascular perfusion in idiopathic dilated cardiomyopathy.

BACKGROUND: The aim of this study was to evaluate tissue-level perfusion in patients with idiopathic dilated cardiomyopathy (IDC), using the myocardial blush grade technique. METHOD: The study population consisted of 26 prospectively enrolled IDC patients (15 women and 11 men; mean age, 59+/-8.8 years) and 26 control subjects (11 women and 15 men; mean age, 54.9+/-10.6 years), whose angiographic films were technically adequate for myocardial blush grade analysis. After grading, we measured total blush score (TBS) for both groups. TBS was determined as the sum of the blush grades of each coronary territory. RESULTS: A total of 156 coronary territories in both groups were assessed. Average of TBS was significantly lower in patients with IDC than in control group (7.6+/-1.2 vs. 8.8+/-0.4; P<0.0001). The TBS significantly and inversely correlated with New York Heart Association class, heart rate, left ventricular end-systolic dimension, and left ventricular end-diastolic pressure, and positively correlated with left ventricular ejection fraction (r=-0.76, P<0.001; r=-0.61, P=0.001; r=-0.77, P<0.0001; r=-0.68, P<0.0001; and r=0.67, P<0.0001, respectively). CONCLUSION: In IDC, decreased TBS might be assumed to be a surrogate marker for a diseased microvascular network in the catheterization laboratory. The relationship between reduced TBS and IDC severity suggests that this index might have prognostic significance.

A novel angiographic methodology for the quantification of angiogenesis.

The objective is to develop a method to quantify the dynamic information of contrast transport using angiography for investigating angiogenic treatments. In the rabbit hindlimb ischemia model, contrast media transport was examined for both arteries and the microvasculature. Time histories of image intensity were constructed and modeled. The differences in contrast transport quantified by the parameters of the mathematical model were statistically compared between animals treated with an adenoviral vector that expressed vascular endothelial growth factor and untreated animals. The data reveal that after one week of ischemia, treated animals have a statistical increase in the number of large vessels that convect blood more efficiently. This analysis further shows a statistically significant increase in the angiographic blush in the treated animals. A methodology is described that offers the capability of examining the number and geometry of large arteries, the dynamics of contrast transport, and the amount of angiographic blush that is related to microvascular density. In therapeutic angiogenesis, numerous techniques are used to measure variables such as the angiographic score, capillary density, and regional blood flow. The analysis presented herein can offer information of these variables, and is transferable from the laboratory to the clinical arena.

Molecular imaging and ultrasound-assisted drug delivery.

Ultrasound imaging is undergoing a major revolution, about to bring this modality well beyond its established role as a low-cost noninvasive real-time imaging modality. Particularly important has been the commercial availability of microbubble-based contrast agents. Several new indications for contrast ultrasound have been developed and have entered clinical practice. The characterization of focal liver lesions and the follow-up of antiangiogenic therapy are two applications that will have a major impact in medical practice. Others, such as prostate cancer diagnosis, are still under investigation and need to be clinically validated. Thanks to its outstanding sensitivity, contrast-enhanced ultrasound is also geared to become the preferred modality for molecular imaging of diseases occurring at the vascular level. Angiogenesis, inflammation, and other endothelial dysfunctions are important targets that can be imaged and investigated with targeted microbubbles. In the field of prostate cancer, targeted agents will facilitate detection and provide additional information on tumor size, and hopefully on aggressiveness as well. Ultrasound can also play a role to deliver drugs or genes locally. This is an exciting area that has become an important field of research. Imaging and drug delivery can be performed simultaneously, thereby achieving the release of a drug, at the site where it is needed, in a most efficient way.

Assessment of coronary blood flow and the reactivity of the microcirculation non-invasively with transthoracic echocardiography.

BACKGROUND: The development in ultrasound technology has allowed the use of non-invasive transthoracic echocardiography (TTE) for the study of coronary artery physiology and pathophysiology. TTE can be used to detect atherosclerotic changes in epicardial coronary arteries and to study the effects of specific interventions on coronary microcirculation. AIM: The purpose of this review was to summarize the development of TTE, and outweigh the strenghts and weaknesses of the method for the evaluation of coronary artery blood flow. Moreover, findings from clinical trials studying microcirculatory reactivity using TTE are presented. CONCLUSIONS: TTE is a feasible and reproducible method for the evaluation of coronary artery blood flow. It can also be used in assessing the vasodilation of the epicardial coronary artery simultaneously with flow velocity measurement during the cold pressor test and coronary flow velocity reserve assessment. It is specifically suitable for repeated measurements in interventional trials.

Microcirculation volumetric flow assessment using high-resolution, contrast-assisted images.

To improve the resolution of contrast-assisted imaging systems, we previously developed a 25-MHz microbubbles-destruction/replenishment imaging system with a spatial resolution of 160 X 160 microm. The goal of the present study was to propose a new approach for functionally evaluating the microvascular volumetric blood flow based on this high-frequency, ultrasound imaging system. The approach includes locating the perfusion area and estimating the blood flow velocity therein. Because the correlation changes between before and after microbubble destruction in two adjacent images, a correlated-based approach was introduced to detect the blood perfusion area. We also have derived a new sigmoid-based model for characterizing the microbubbles replenishment process. Two parameters derived from the sigmoid-based model - the rate constant and inflection time - were adopted to evaluate the blood flow velocity. This model was validated using both simulations and in vitro experiments for mean flow velocities ranging from 1 to 10 mm/s, which showed that the model was in good agreement with simulated and measured microbubble-replenishment time-intensity curves. The results indicate that the actual flow velocity is highly correlated with the estimates of the rate constant and the reciprocal of the inflection time. B-mode imaging experiments for mean flow velocities ranging from 0.4 to 2.1 mm/s were used to assess the volumetric flow in the microcirculation. The results indicated the high correlation between the actual volumetric flow rate and the product of the estimated perfusion area and rate constant, and the reciprocal of the inflection time. We also found that the boundary of the microbubble destruction volume significantly affected estimations of the flow velocity. The perfusion area can be located, and the corresponding flow velocity can be estimated simultaneously in a one-stage, microbubble-destruction/replenishment process, which makes the assessment of the volumetric bloo- d flow in the microcirculation feasible using a real-time, high-frequency ultrasound system.

Contrast harmonic ultrasound and indocyanine-green fluorescence video angiography for evaluation of dermal and subdermal microcirculation in free parascapular flaps.

PURPOSE: Contrast harmonic ultrasound (CHI) with a linear transducer is a new diagnostic approach that allows dynamic and quantitative flow detection of tissue perfusion in microsurgery. The aim of the study was the evaluation of perfusion of the dermal and subdermal layers of microvascular tissue transplants with CHI in comparison to ICG-fluorescence angiography. MATERIAL AND METHOD: In a prospective clinical study indocyanine-green fluorescence video angiography and contrast enhanced high resolution ultrasound (5-10 MHz; linear transducer; Logiq 9; GE) were used for evaluation of the microcirculation in 10 transplanted free parascapular flaps. Two regions were analysed, the centre of the flap and the region of the anastomosis. The perfusion patterns of both methods were compared. RESULTS: The perfusion indexes measured by ICG-fluorescence angiography correlated very precisely in all patients with the quantitative perfusion curves of contrast-enhanced US with CHI. Two flaps with slow filling and low dye intensity showed low contrast enhancement in CHI with modified perfusion curves with slow increase. In two cases a reduced perfusion and filling were found. There were no statistical differences between the two diagnostic methods (p>0.01). CONCLUSION: CHI improves US detections of dermal and subdermal microcirculation in comparison to ICG fluorescence angiography. CHI is a new diagnostic method for postoperative monitoring of free flaps.

Contrast harmonic ultrasound and indocyanine-green fluorescence video angiography for evaluation of dermal and subdermal microcirculation in free parascapular flaps.

PURPOSE: Contrast harmonic ultrasound (CHI) with a linear transducer is a new diagnostic approach that allows dynamic and quantitative flow detection of tissue perfusion in microsurgery. The aim of the study was the evaluation of perfusion of the dermal and subdermal layers of microvascular tissue transplants with CHI in comparison to ICG-fluorescence angiography. MATERIAL AND METHOD: In a prospective clinical study Indocyanine-Green Fluorescence Video Angiography and Contrast Enhanced High Resolution Ultrasound (5-10 MHz; linear transducer; Logiq 9; GE) were used for evaluation of the microcirculation in 10 transplanted free parascapular flaps. Two regions were analysed, the centre of the flap and the region of the anastomosis. The perfusion patterns of both methods were compared. RESULTS: The perfusion indexes measured by ICG-fluorescence angiography correlated very precisely in all patients with the quantitative perfusion curves of contrast-enhanced US with CHI. Two flaps with slow filling and low dye intensity showed low contrast enhancement in CHI with modified perfusion curves with slow increase. In two cases a reduced perfusion and filling were found. There were no statistical differences between the two diagnostic methods (p>0.01). CONCLUSION: CHI improves US detections of dermal and subdermal microcirculation in comparison to ICG fluorescence angiography. CHI is a new diagnostic method for postoperative monitoring of free flaps.

[Laser Doppler flowmetry in differential diagnosis of organic erectile dysfunction].

The aim of this study was to investigate penile microcirculation in patients with erectile dysfunction. Laser doppler flowmetry was performed in 67 patients (mean age 43.9 +/- 1.53 years) with organic erectile dysfunction and in 20 men without erectile dysfunction. It was found that in patients with arteriogenic erectile dysfunction blood flow parameters were subnormal including flux motions. The occlusive test revealed reduced postocclusive reactive hyperemia in patients with arteriogenic erectile dysfunction. Patients with neurogenic erectile dysfunction have signs of sympathetic denervation of microcirculation and decreased respiratory response.

[Combined treatment of complicated chlamydial infection in males with ozone therapy].

Urogenital chlamydial monoinfection was diagnosed in 127 males using enzyme immunoassay, polymerase chain reaction, transrectal ultrasound examination of the prostatic gland. Of them, 72 patients had chronic urethroprostatitis. Microhemodynamics of these patients was studied with laser doppler flowmetry of the prostate and urethra. The patients received etiotropic therapy with fromilide, regional transurethral and transrectal ozone therapy. The symptoms relieved in 4-6 weeks. Repeated enzyme immunoassay and polymerase chain reaction stated elimination of the infective agent. Improvement of hemodynamics and urethral, prostatic microcirculation was stated after administration of regional ozone therapy.

Characterization of circulatory disorders in beta-thalassemic mice by noninvasive ultrasound biomicroscopy.

Beta-thalassemia is an inherited hematological disease caused by a decrease or absence of production of beta-globin that requires chronic therapeutic interventions. This condition leads to important arterial and venous thromboembolic events, transitory ischemic attacks, and microcirculatory obstructions, indicative of circulatory disturbances. To investigate the presence of microcirculatory disorders without the confounding effect of treatments, we used beta-thalassemic mice with typical clinical characteristics of human beta-thalassemia major. One impediment to the understanding of microcirculatory physiology, in particular for beta-thalassemic mice, has been the lack of an appropriate noninvasive imaging approach. We thus developed a novel noninvasive high-frequency ultrasound imaging method to evaluate murine vascular hemodynamic properties. In our beta-thalassemic mice, total peripheral vascular resistance was significantly increased (P < 0.01) compared with wildtype littermates, whereas mean blood pressure, heart rate, and cardiac output were similar (P = nonsignificant). Importantly, the vascular hemodynamics in beta-thalassemic mice were significantly affected according to the Pourcelot indexes measured in the common carotid artery and abdominal aorta (P < 0.01 and P < 0.05, respectively). Hence, our beta-thalassemia characterization of vascular hemodynamics by noninvasive ultrasonic approaches proves the existence and provides unique quantitative assessment of microcirculatory flow disturbances in those mice.

Association between serum gamma-glutamyltransferase levels and coronary microvascular function in hypertensive patients.

OBJECTIVE: Serum gamma-glutamyltransferase (GGT) level is an independent risk factor for cardiovascular (CV) disease, and there is a strong association between serum GGT levels and most CV risk factors, including hypertension; however, the role of serum GGT level as an independent risk factor for target organ damage in hypertension remains controversial. Accordingly, we aimed to determine whether serum GGT level is independently and specifically associated with coronary flow reserve (CFR) impairment in hypertensive patients. METHODS: We examined 100 never-treated and newly diagnosed hypertensive individuals, and CFR was achieved in 97 (97%) of them. They were divided into two groups based on serum GGT levels. RESULTS: Subjects with higher GGT had significantly impaired CFR as compared to those with lower GGT (2.10 +/- 0.36 versus 2.57 +/- 0.54, P < 0.0001). After adjusting for potential confounders, including age, sex, body mass index, blood pressure, lipids and glucose, we found that serum GGT levels were independently associated with CFR impairment (beta = -0.62, P < 0.0001). We also found that GGT level was a good predictor of low CFR at the receiver-operating characteristic curve. Area under the curve was 79% [95% confidence interval: 0.70-0.88], and GGT level was significantly predictive of low CFR (P < 0.0001). CONCLUSION: These results support a role for serum GGT level as an independent marker of target organ damage in hypertensive subjects without concomitant risk factors.

Application of 99mTc-pertechnetate scintigraphy to microvascular autologous transplantation of the submandibular gland in patients with severe keratoconjunctivitis sicca.

UNLABELLED: Our objective was to evaluate the role of (99m)Tc-pertechnetate scintigraphy on microvascular autologous transplantation of the submandibular gland in patients with severe keratoconjunctivitis sicca (KCS). METHODS: (99m)Tc-Pertechnetate scintigraphy was performed on 106 patients with severe KCS. The patients were examined before surgery and at 1 wk and 3 mo afterward using a standardized protocol that included static scintigrams, time-activity curves, and delayed scintigrams to check the function and secretion of the major salivary glands. The scintigraphic findings were assessed visually. When possible, the scintigraphic findings were compared with the clinical appearance of the transplanted gland. RESULTS: The function of all 4 major salivary glands was almost completely lost in 10 patients, indicating that these patients were not suitable for transplantation. The other 96 patients were treated by autologous transplantation of the submandibular gland. In 14 patients, the function of the major salivary glands was below normal. One patient's scintigram, obtained on the second day after surgery, showed no uptake of (99m)Tc-pertechnetate in the transplanted gland. Surgical exploration showed embolism of the artery of the transplanted gland. Scintigraphy was performed 1 wk after surgery in 90 patients. There was no uptake of (99m)Tc-pertechnetate in the temporal region in 8 patients, indicating that the glands were not revascularized. Scintigraphy showed obvious uptake of (99m)Tc-pertechnetate in the temporal region of the other 82 patients, indicating that the transplanted glands were viable. At more than 3 mo after surgery, scintigraphy was again performed on 30 patients. Scintigraphy after a 120-min delay showed that (99m)Tc-pertechnetate drained into the orbit through the duct of the transplanted gland in 26 patients. However, no secretion into the orbit was found in 4 patients, indicating obstruction of the duct. CONCLUSION: Scintigraphy plays an important role in microvascular autologous transplantation of the submandibular gland in patients with severe KCS. Scintigraphy can be used to select patients and donor glands, to evaluate the viability of the graft, and to check the patency of Wharton's duct of the transplanted gland.

Spatial heterogeneity of low-grade gliomas at the capillary level: a PET study on tumor blood flow and amino acid uptake.

UNLABELLED: Many low-grade gliomas (World Health Organization grade II) respond to chemotherapy. Cerebral blood flow (CBF) and microvessel density may be critical for drug delivery. We used PET with (18)F-fluoro-ethyl-l-tyrosine (FET) to measure the spatial distribution of the amino acid carrier, which is located at the brain capillaries, and (15)O-H(2)O to measure tumor CBF. METHODS: Seventeen patients with low-grade glioma were studied. Region-of-interest (ROI) analysis was used to quantify tumor tracer uptake, which was normalized to cerebellar uptake (tumor-to-cerebellum ratio). "Active" tumor was defined as tumor having a radioactivity concentration that was at least 110% of the cerebellar activity. This threshold provided measures of active tumor volume, global and peak tumor CBF, and (18)F-FET uptake. Trace ROIs were applied to create voxelwise profiles of CBF and (18)F-FET uptake across tumor and brain. Standard MRI sequences were used for spatial correlations. RESULTS: Fourteen of 17 tumors showed increased global CBF and (18)F-FET uptake. Active tumor volumes ranged between 3 and 270 cm(3) for (18)F-FET and between 1 and 41 cm(3) for CBF. Global (18)F-FET uptake in tumors corresponded to CBF increases (Spearman rank rho = 0.771, P < 0.01). The volumes of increased CBF and (18)F-FET uptake spatially coincided and were also correlated (rho = 0.944, P < 0.01). Trace ROIs showed that irrespective of increased (18)F-FET uptake at the tumor periphery, CBF increases were more confined to the tumor center. Within individual tumors, spatial heterogeneity was present. Particular tumors infiltrating the corpus callosum showed low CBF and (18)F-FET uptake in this tumor region. The patterns observed with PET were not reflected on MRI of the tumors, all of which presented as homogeneous non-gadolinium-enhancing lesions. CONCLUSION: Low-grade gliomas are heterogeneous tumors with regard to the distribution of amino acid uptake and CBF. Both are coupled in the tumor center. At the tumor periphery, where tumor infiltration of surrounding brain occurs, CBF may be low irrespective of increased (18)F-FET uptake. An ongoing study is investigating the effect of chemotherapy on these observations.

Improved visualization of vessels and hepatic tumors by micro-computed tomography (CT) using iodinated liposomes.

OBJECTIVE: The goal of this study was to determine whether iodinated liposomes are a suitable tracer for mice microvessel and liver imaging by preclinical computed tomography (CT). MATERIALS AND METHODS: Iodinated liposomes were evaluated for vessel and liver imaging. A first group of nude mice was imaged by micro-CT after i.v. injection of liposomes at 1 or 2 gI/kg body weight (b.w.) for intervals up to 24 hours. A second group of mice bearing liver micrometastases was imaged after injection of liposomes at 2 gI/kg b.w. for intervals up to 24 hours. RESULTS: Vascular enhancements of 120 +/- 8 and 322 +/- 20 Hounsfield unit (HU) were obtained after injection of liposomes at 1 or 2 gI/kg b.w., respectively. This enhancement decreased with a blood half-life of 135 +/- 10 and 86 +/- 9 minutes, respectively. Liver enhancement of 157 +/- 5 and 235 +/- 23 HU were obtained after injection of iodinated liposomes at 1 and 2 gI/kg b.w., respectively. Liver micrometastases (250 microm) were detectable after injection of iodinated liposomes at 2 gI/kg b.w. CONCLUSIONS: Iodinated liposomes are a suitable contrast agent for vessels and liver imaging by micro-CT allowing clear vascular enhancement and detection of small liver metastases.