Chemical exchange saturation transfer MRI contrast in the human brain at 9.4 T.

PURPOSE: The high chemical shift separation at 9.4 T allows for selective saturation of proton pools in exchange with water protons. For the first time, highly selective and comprehensive chemical exchange saturation transfer (CEST) experiments were performed in the human brain at 9.4 T. This work provides insight into CEST signals in the human brain in comparison with existing animal studies, as well as with CEST effects in vivo at lower field strengths. METHODS: A novel snapshot-CEST method for human brain scans at 9.4 T was optimized and employed for highly-spectrally-resolved (95 offsets) CEST measurements in healthy subjects and one brain tumor patient. Reproducibility and stability between scans was verified in grey and white matter after B0, B1, and motion correction of the acquired 3D CEST volumes. Two-step Lorentzian fitting was used to further improve separation of spectrally discernible signals to create known and novel CEST contrast maps at 9.4 T. RESULTS: At a saturation power of B1 = 0.5 µT most selective CEST effects could be obtained in the human brain with high inter-scan reproducibility. While contrast behavior of previously measured signals at lower field, namely amide-, guanidyl- and NOE-CEST effects, could be reproduced, novel signals at 2.7 ppm, and -1.6 ppm could be verified in healthy subjects and in a brain tumor patient for the first time. CONCLUSION: High spectral resolution chemical exchange saturation transfer at 9.4 T allows deeper insights into the Z-spectrum structure of the human brain, and provides many different contrasts showing different correlations in healthy tissue and in tumor-affected areas of the brain, generating hypotheses for future investigations of in-vivo-CEST at UHF.

Intraspinal intradural nodular fasciitis mimicking glioblastoma metastasis: a case report.

We report the case of a 78-year-old male patient suffering from right temporal glioblastoma with radiographic meningeal tumor spread. During the further course of the disease he developed a rapidly progressive paraplegia. An magnetic resonance imaging scan showed a contrast enhancing an intraspinal intradural lesion with compression of the myelon on segment Th 8/9. With a high suspicion of a spinal metastasis of the known glioblastoma, emergency spinal decompression and resection of the intradural mass was performed. However, histopathological evaluation revealed nodular fasciitis without any signs of glial origin.

Minimally invasive neurosurgery for vascular lesions.

Intracranial vascular lesions are known to affect 2% to 4% of the population, predisposing those affected to a lifetime risk of hemorrhagic stroke, ischemia, focal neurologic deficits, or epileptic seizures. These lesions constitute a heterogeneous group, with different lesion types characterized by distinct biologic mechanisms of pathogenesis and progression. In this article, the minimally invasive management of intracranial aneurysms, arteriovenous malformations including arteriovenous fistulas, and cavernous malformations are discussed.

Omovertebral bone associated with Sprengel deformity and Klippel-Feil syndrome leading to cervical myelopathy.

The unusual association of an omovertebral bone with Sprengel deformity and Klippel-Feil syndrome is a complex bone anomaly of unknown incidence and etiology. However, several cases of this rare disease pattern have been reported in the literature. In this paper, the authors present the case of a 34-year-old woman with a 5-month history of progressive gait ataxia and intermittent urinary incontinence, which was found to be caused by aberrant bone growth into the spinal canal from an omovertebral bone that extended from the left scapula pressing into the C-6 vertebral arch and subsequently causing cervical myelopathy. The patient underwent isolated resection of the omovertebral bone and decompression of the spinal canal, and her functional and neurological outcome was favorable.

Usefulness of pressure-controlled ventilation at high inspiratory pressures to induce acute lung injury in mice.

Acute lung injury (ALI), as occurs with prolonged mechanical ventilation, contributes to morbidity and mortality of critical illness, and studies on novel genetic or pharmacological targets are areas of intense investigation. Here, we systematically tested a murine model of ALI by using pressure-controlled ventilation to induce ventilator-induced lung injury. For this purpose, C57BL/6 or Sv129 mice were anesthetized and underwent tracheotomy followed by induction of ALI via mechanical ventilation. Mice were ventilated in a pressure-controlled setting at different inspiratory pressure levels (15-45 mbar) and over different times (0-90 min, 100% oxygen). As outcome parameters, we assessed pulmonary edema (wet-to-dry ratios), bronchoalveolar fluid albumin content, pulmonary myeloperoxidase activity, macrophage inflammatory protein-2, and pulmonary gas exchange. These studies revealed maximal differences in severity of lung injury between different mouse strains after 90 min of ventilation time at 45 mbar. Use of lower concentrations of inspired oxygen did not alter disease severity. Increases of CD73 transcript (5'-ectonucleotidase, pacemaker of extracellular adenosine production) or total pulmonary adenosine levels with mechanical ventilation were less pronounced in C57BL/6 mice, suggesting attenuated adenosine protection in C57BL/6 mice. Together, these studies demonstrate feasibility of this model to induce murine ALI.

Identification of ectonucleotidases CD39 and CD73 in innate protection during acute lung injury.

Acute lung injury (ALI), such as that which occurs with mechanical ventilation, contributes to morbidity and mortality of critical illness. Nonetheless, in many instances, ALI resolves spontaneously through unknown mechanisms. Therefore, we hypothesized the presence of innate adaptive pathways to protect the lungs during mechanical ventilation. In this study, we used ventilator-induced lung injury as a model to identify endogenous mechanisms of lung protection. Initial in vitro studies revealed that supernatants from stretch-induced injury contained a stable factor which diminished endothelial leakage. This factor was subsequently identified as adenosine. Additional studies in vivo revealed prominent increases in pulmonary adenosine levels with mechanical ventilation. Because ectoapyrase (CD39) and ecto-5'-nucleotidase (CD73) are rate limiting for extracellular adenosine generation, we examined their contribution to ALI. In fact, both pulmonary CD39 and CD73 are induced by mechanical ventilation. Moreover, we observed pressure- and time-dependent increases in pulmonary edema and inflammation in ventilated cd39(-/-) mice. Similarly, pharmacological inhibition or targeted gene deletion of cd73 was associated with increased symptom severity of ventilator-induced ALI. Reconstitution of cd39(-/-) or cd73(-/-) mice with soluble apyrase or 5'-nucleotidase, respectively, reversed such increases. In addition, ALI was significantly attenuated and survival improved after i.p. treatment of wild-type mice with soluble apyrase or 5'-nucleotidase. Taken together, these data reveal a previously unrecognized role for CD39 and CD73 in lung protection and suggest treatment with their soluble compounds as a therapeutic strategy for noninfectious ALI.