Effect of bilateral carotid occlusion on cerebral hemodynamics and perivascular innervation: An experimental rat model.

We aimed to investigate the effect of chronic cerebral hypoperfusion on cerebral hemodynamics and perivascular nerve density in a rat model. Bilateral common carotid artery (CCA) ligation (n = 24) or sham-operation (n = 24) was performed with a 1-week interval. A subgroup (ligated n = 6; sham-operated n = 3) underwent magnetic resonance imaging (MRI) before the procedures and 2 and 4 weeks after the second procedure. After termination, carotids were harvested for assessment of complete ligation and nerve density in cerebral arteries that were stained for the general neural marker PGP 9.5 and sympathetic marker TH by computerized image analysis. Five rats were excluded because of incomplete ligation. MRI-based tortuosity of the posterior communicating artery (Pcom), first part of the posterior cerebral artery (P1) and basilar artery was observed in the ligated group, as well as an increased volume (p = 0.05) and relative signal intensity in the basilar artery (p = 0.04; sham-group unchanged). Immunohistochemical analysis revealed that compared to sham-operated rats, ligated rats had increased diameters of all intracircular segments and the extracircular part of the internal carotid artery (p < 0.05). Ligated rats showed a higher general nerve density compared to controls in P1 (10%, IQR:8.7-10.5 vs. 6.6%, IQR:5.5-7.4, p = 0.003) and Pcom segments (6.4%, IQR:5.8-6.5 vs. 3.2%, IQR:2.4-4.3, p = 0.003) and higher sympathetic nerve density in Pcom segments (3.7%, IQR:2.8-4.8 vs. 1.7%, IQR:1.3-2.2, p = 0.02). Bilateral CCA occlusion resulted in redistribution of blood flow to posteriorly located cerebral arteries with remarkable changes in morphology and perivascular nerve density, suggesting a functional role for perivascular nerves in cerebral autoregulation.

Improved estimation of MR relaxation parameters using complex-valued data.

PURPOSE: In MR image analysis, T1 , T2 , and T2* maps are generally calculated using magnitude MR data. Without knowledge of the underlying noise variance, parameter estimates at low signal to noise ratio (SNR) are usually biased. This leads to confounds in studies that compare parameters across SNRs and or across scanners. This article compares several estimation techniques which use real or complex-valued MR data to achieve unbiased estimation of MR relaxation parameters without the need for additional preprocessing. THEORY AND METHODS: Several existing and new techniques to estimate relaxation parameters using complex-valued data were compared with widely used magnitude-based techniques. Their bias, variance and processing times were studied using simulations covering various aspects of parameter variations. Validation on noise-degraded experimental measurements was also performed. RESULTS: Simulations and experiments demonstrated the superior performance of techniques based on complex-valued data, even in comparison with magnitude-based techniques that account for Rician noise characteristics. This was achieved with minor modifications to data modeling and at computational costs either comparable to or higher ( ≈two fold) than magnitude-based estimators. Theoretical analysis shows that estimators based on complex-valued data are statistically efficient. CONCLUSION: The estimation techniques that use complex-valued data provide minimum variance unbiased estimates of parametric maps and markedly outperform commonly used magnitude-based estimators under most conditions. They additionally provide phase maps and field maps, which are unavailable with magnitude-based methods. Magn Reson Med 77:385-397, 2017. © 2016 Wiley Periodicals, Inc.

MRI of hip prostheses using single-point methods: in vitro studies towards the artifact-free imaging of individuals with metal implants.

Use of magnetic resonance imaging (MRI) in individuals with orthopedic implants is limited because of the large distortions caused by metallic components. As a possible solution for this problem, we suggest the use of single-point imaging (SPI) methods, which are immune to the susceptibility artifacts observed with conventional MRI methods. A further advantage of SPI, based on the fact that signal encoding is achieved in ultra-short times (as short as tens of microseconds), is that they enable the direct visualization of the polymeric elements of the implants, allowing the detection of possible implant failures. We present in vitro SPI images of polymeric sockets of two hip prostheses together with artifact-free images of gelatin phantoms containing their respective metallic stems. These data underscore the great potential of the SPI technique for obtaining artifact-free images of individuals with large metal implants.

Transmural gradients of cardiac myofiber shortening in aortic valve stenosis patients using MRI tagging.

Aortic valve stenosis impairs subendocardial perfusion with a risk of irreversible subendocardial tissue damage. A likely precursor of damage is subendocardial contractile dysfunction, expressed by the parameter TransDif, which is defined as epicardial minus endocardial myofiber shortening, normalized to the mean value. With the use of magnetic resonance tagging in two short-axis slices of the left ventricle (LV), TransDif was derived from LV torsion and contraction during ejection. TransDif was determined in healthy volunteers (control, n = 9) and in patients with aortic valve stenosis before (AVSten, n = 9) and 3 mo after valve replacement (AVRepl, n = 7). In the control group, TransDif was 0.00 +/- 0.14 (mean +/- SD). In the AVSten group, TransDif increased to 0.96 +/- 0.62, suggesting impairment of subendocardial myofiber shortening. In the AVRepl group, TransDif decreased to 0.37 +/- 0.20 but was still elevated. In eight of nine AVSten patients, the TransDif value was elevated individually (P < 0.001), suggesting that the noninvasively determined parameter TransDif may provide important information in planning of treatment of aortic valve stenosis.

Developmental changes and water status in tulip bulbs during storage: visualization by NMR imaging.

Magnetic Resonance Imaging (MRI) and light and scanning electron microscopy (SEM) were used to follow time-dependent morphological changes and changes in water status of tulip bulbs (Tulipa gesneriana L., cv. 'Apeldoorn') during bulb storage for 12 weeks at 20 degrees C (non-chilled) or 4 degrees C (chilled) and after planting. MR images reflecting the water content, the relaxation times T1 and T2 (or their reciprocal values, the relaxation rates R1 and R2), and the apparent self-diffusion coefficient of water molecules (ADC), were obtained for intact bulbs. After planting, scape elongation and flowering occurred only in chilled bulbs, while elongation in non-chilled bulbs was retarded. Microscopic observations showed different structural components and high heterogeneity of the bulb tissues. MRI revealed the elongation of the flower bud during storage, which was significantly faster in the chilled bulbs. In addition, MRI demonstrated a redistribution of water between different bulb organs, as well as significant differences in the pattern of this redistribution between the chilled and non-chilled bulbs. Generally, R2 relaxation rates became faster in all bulb organs during storage. At the same time, ADC values remained constant in the chilled bulbs, while exhibiting a significant increase in the non-chilled bulbs.

Effect of carbogen breathing on the physiological profile of human glioma xenografts.

The aim of this study was to evaluate the effect of carbogen breathing on the physiological profile of human glioma xenografts. Near infrared spectroscopy was used to investigate changes in oxy- and deoxyhemoglobin concentrations in tumor blood. Oxygen tension changes in tumor tissue were evaluated by (19)F-MR relaxometry, using perfluoro-15-crown-5-ether, and modifications of tumor blood perfusion (TBP) were analyzed by fast dynamic (1)H-MR imaging of Gd-DTPA uptake. Finally, changes of the bioenergetic status and pH of tumor cells were analyzed by (31)P-MRS. After 5 to 8 min of carbogen breathing, the average oxygen tension increase in tumor tissue was 4.6 +/- 1.3 mm Hg, which is in agreement with an increase of the oxyhemoglobin concentration in tumor blood (Delta[O(2)Hb] = 9. 2 +/- 3 microM). However, simultaneously the TBP was reduced, the bioenergetic status was diminished, and pH was decreased. As 100% O(2) breathing alone did not result in a detectable increase of oxyhemoglobin in tumor blood, the increase of the tumor oxygenation by carbogen appears to be mediated by its CO(2) content. This component may cause a nutrient-limited decrease of oxidative energy metabolism, indirectly via a steal-effect and/or by inhibition of the glycolytic rate resulting from tissue acidification. Magn Reson Med 42:490-499, 1999.

Diffusion of metabolites in normal and ischemic rat brain measured by localized 1H MRS.

The apparent diffusion coefficient (ADC) of choline-containing compounds (Cho), creatine and phosphocreatine (Cre), N-acetyl-aspartate (NAA), lactate, and water was measured in normal rat brain, and in the ischemic and contralateral region of rat brain approximately 3 and 24 h after induction of focal cerebral ischemia. After 3 h of ischemia, the ADC of Cre and NAA in the ischemic region had significantly decreased by 29% and 19%, respectively (P < 0.05). Lactate ADC was also obtained in the ischemic region. After 24 h of focal ischemia, no ADC values could be measured for NAA, Cre and Cho in the ischemic region because their concentrations had become too low. The ADCs of lactate and water in the ischemic volume were virtually identical at 3 and 24 h after occlusion. The experiments suggest that the ADC decrease of water after induction of ischemia is partly caused by changes in the diffusion characteristics of the intracellular compartment.

Dynamic changes in water ADC, energy metabolism, extracellular space volume, and tortuosity in neonatal rat brain during global ischemia.

To obtain a better understanding of the mechanisms underlying early changes in the brain water apparent diffusion coefficient (ADC) observed in cerebral ischemia, dynamic changes in the ADC of water and in the energy status were measured at postnatal day 8 or 9 in neonatal rat brains after cardiac arrest using 1H MRS/MRI and 31P MRS, respectively. The time courses of the MR parameters were compared with changes in the extracellular space (ECS) volume fraction (alpha) and tortuosity (lambda), determined from concentration-time profiles of tetramethylammonium applied by iontophoresis. The data show a decrease of the ADC of tissue water after induction of global ischemia of which the time course strongly correlates with the time course of the decrease in the ECS volume fraction and the increase in ECS tortuosity. This indicates that cell swelling is an important cause for the ADC decrease of water.

Status of the neonatal rat brain after NMDA-induced excitotoxic injury as measured by MRI, MRS and metabolic imaging.

Intrastriatal injection of the excitotoxin N-methyl-D-aspartate (NMDA) in neonatal rat brain resulted in an acute ipsilateral decrease of the apparent diffusion coefficient (ADC) of brain tissue water, as measured with diffusion-weighted MRI. The early diffusion changes were accompanied by only mild changes in the overall metabolic status as measured by in vivo 1H MRS and 31P MRS and metabolic imaging of brain sections. Minimal decreases in the high-energy phosphate levels and a small hemispheric acidosis were observed in the first 6 h after NMDA administration. In addition, there was very modest lactate accumulation. Twenty-four hours after the induction of the excitotoxic injury the tissue energy status was still only moderately affected, whereas an overall decrease of 1H MRS-detected brain metabolites was found. Treatment with the non-competitive NMDA-antagonist MK-801 given within 90 min after NMDA injection rapidly reversed the NMDA-induced changes in the entire ipsilateral hemisphere. The effect of the competitive NMDA-antagonist D-CPPene was restricted to the cortical areas and was accomplished on a slower time scale. Our results indicate that; (i) early excitotoxicity in the neonatal rat brain does not lead to profound changes in the metabolic status; and (ii) brain tissue water ADC changes are not necessarily associated with a metabolic energy failure.

Dynamic magnetic resonance imaging and spectroscopie of experimental brain injury.

This article describes the use of non-invasive magnetic resonance (MR) methods for the characterization and monitoring of the pathophysiology of experimental brain injury in laboratory animals as a function of time and treatment. The impact of MR in brain research is primarily due to its non-invasive nature, thereby enabling repeated measurements in long-term studies, and due to the type of information that it provides. MR imaging (MRI) enables the measurement of the morphology/anatomy as well as the functional status of tissues under in vivo conditions. Compared to other in vivo imaging modalities, MRI has a high spatial resolution and allows for a remarkable soft tissue differentiation. MR spectroscopy (MRS) provides information on the biochemical/metabolic status of tissues. MR methods which have proven valuable in animal studies, can be readily translated to the clinical situation where MR-based diagnosis and treatment planning play a rapidly increasing role. After a short introduction into the principles of MR, we will illustrate the remarkable versatility of MR in research on brain injury from recent animal studies. Examples will be mainly drawn from experiments on early injury in focai cerebral ischemia and from research on mechanical brain trauma and excitotoxic lesions. The article ends with a brief description of the perspectives of MR in neuropsychiatry.

In vivo diffusion spectroscopy. An overview.

This review describes in vivo NMR measurements of metabolite diffusion. NMR spectroscopy can employ a variety of endogenous marker molecules to obtain information on various aspects of in vivo biochemistry and biophysics from the diffusion characteristics of these markers. NMR-based metabolite diffusion data give an insight into the physico-chemical properties of the intracellular compartment and of changes therein in relation to development and pathology. Recent applications have proven that in vivo diffusion spectroscopy provides exciting opportunities to both fundamental and applied research.

T1 and T2 relaxation times of the major 1H-containing metabolites in rat brain after focal ischemia.

The relaxation properties of water and metabolites were measured in rat brain following the occlusion of the middle cerebral artery (MCA) with localized 1H MRS. The PRESS sequence was employed to select volumes of 39 microL in the ischemic and the contralateral hemisphere. T1 and T2 relaxation times and peak intensities of water, choline containing compounds (Cho), creatine and phosphocreatine (Cre) and N-acetyl aspartate (NAA) in both hemispheres were determined at 3-6 h, 1 day and 3 or 4 days after occlusion. Lactate in the ischemic hemisphere was also quantified. The relaxation properties and peak intensities of NAA, Cre and Cho remained unchanged in the ischemic volume during the first 3-6 h of ischemia as compared to the contralateral volume. Water T2 was slightly increased in the ischemic volume. After 24 h the T1 and T2 of water and Cre and the T1 of Cho had increased significantly in the ischemic volume, while the peak intensities of Cho, Cre and NAA were reduced. It appears therefore that tissue changes which occur in the early phase of ischemia have no significant effects on the relaxation behaviour of the metabolites. However, ischemic brain damage affects the relaxation behaviour and concentration of the metabolites and water at later stages.

Changes in metabolites and tissue water status after focal ischemia in cat brain assessed with localized proton MR spectroscopy.

Localized proton spectroscopy was used to monitor changes in metabolism and the biophysical status of tissue water in cat brain induced by occlusion of the middle cerebral artery. Changes in the intensity of N-acetyl-aspartate (NAA), total creatine (tCr), and lactate (Lac) signals in localized volumes of interest in the ischemic hemisphere were quantified relative to the preischemic signal. Changes in the apparent diffusion coefficient (ADC), T1- and T2-relaxation times of water in those volumes were also quantified. Lactate was shown to increase rapidly in the first 0.5-2.0 h of ischemia and stabilized afterwards. The ADC of water started to decrease from 0.64 x 10(-9) m2/s to 0.54 x 10(-9) m2/s in the first minutes following occlusion, as was shown in two cases where ADC was measured with high temporal resolution, and stabilized after approximately 3 h at 0.38 x 10(-9) m2/s (n = 6). NAA and tCr decreased by 35% (P < 0.0001) and 30% (P < 0.005), respectively, in the first 8 h of ischemia in comparison with the preischemic control levels. T1 and T2 gradually increased with 0.3 s (P < 0.0001) and 5.2 ms (P < 0.0001), respectively, during the same time span.