Background: Since the introduction of miltefosine (MIL) as first-line therapy in the kala-azar elimination programme in the Indian subcontinent, treatment failure rates have been increasing. Since parasite infectivity and virulence may become altered upon treatment relapse, this laboratory study assessed the phenotypic effects of repeated in vitro and in vivo MIL exposure. Methods: Syngeneic Leishmania donovani lines either or not exposed to MIL were compared for drug susceptibility, rate of promastigote multiplication and metacyclogenesis, macrophage infectivity and behaviour in the sand fly vector, Lutzomyia longipalpis. Results: Promastigotes of both in vitro and in vivo MIL-selected strains displayed a slightly reduced drug susceptibility that was associated with a reduced MIL-accumulation linked to a lower copy number (disomic state) of chromosome 13 harboring the miltefosine transporter (LdMT) gene. In vitro selected promastigotes showed a lower rate of metacyclogenesis whereas the in vivo derived promastigotes displayed a moderately increased growth rate. Repeated MIL exposure did neither influence the parasite load nor metacyclogenesis in the sand fly vector. Conclusions: Recurrent in vitro and in vivo MIL exposure evokes a number of very subtle phenotypic and genotypic changes which could make promastigotes less susceptible to MIL without attaining full resistance. These changes did not significantly impact on infection in the sand fly vector.
C-arm flat-panel detector computed tomographic (CT) imaging in the angiography suite increasingly plays an important part during interventional neuroradiological procedures. In addition to conventional angiographic imaging of blood vessels, flat detector CT (FD CT) imaging allows simultaneous 3D visualization of parenchymal and vascular structures of the brain. Next to imaging of anatomical structures, it is also possible to perform FD CT perfusion imaging of the brain by means of cerebral blood volume (CBV) or pooled blood volume (PBV) mapping during steady state contrast administration. This enables more adequate decision making during interventional neuroradiological procedures, based on real-time insights into brain perfusion on the spot, obviating time consuming and often difficult transportation of the (anesthetized) patient to conventional cross-sectional imaging modalities. In this paper we review the literature about the nature of FD CT PBV mapping in patients and demonstrate its current use for diagnosis and treatment monitoring in interventional neuroradiology.
30 March 2021 in Journal of Integrative Neuroscience
The technical feasibility and diagnostic potential of angiographic flat-detector perfusion imaging technique, combining digital subtraction angiography with a flat-detector computed tomography steady-state perfusion imaging, was explored in patients treated with direct or indirect revascularization surgery. This short communication is about an imaging modality with great potential for evaluation, comparison and grading of vascular perfusion territory areas and anatomical location selectively perfused by direct and indirect cerebral bypasses.
Pre-operative embolization of hypervascular intracranial tumors can be performed to reduce bleeding complications during resection. Accurate vascular mapping of the tumor is necessary for both the correct indication setting for embolization and for the evaluation of the performed embolization. We prospectively examined the role of whole brain and selective parenchymal blood volume (PBV) flat detector computer tomography perfusion (FD CTP) imaging in pre-operative angiographic mapping and embolization of patients with hypervascular intracranial tumors. Whole brain FD CTP imaging with a contrast injection from the aortic root and selective contrast injection in the dural feeding arteries was performed in five patients referred for tumor resection. Regional relative PBV values were obtained pre- and post-embolization. Total tumor volumes with selective external carotid artery (ECA) supply volumes and post-embolization devascularized tumor volumes were determined as well. In all patients, including four females and one male, with a mean age of 54.2 years (range 44–64 years), the PBV scans were performed without adverse events. The average ECA supply was 54% (range 31.5–91%). The mean embolized tumor volume was 56.5% (range 25–94%). Relative PBV values decreased from 5.75 ± 1.55 before embolization to 2.43 ± 1.70 post-embolization. In one patient, embolization was not performed because of being considered not beneficial for the resection. Angiographic FD CTP imaging of the brain tumor allows 3D identification and quantification of individual tumor feeder arteries. Furthermore, the technique enables monitoring of the efficacy of pre-operative endovascular tumor embolization.
25 December 2023 in Interdisciplinary Neurosurgery
Introduction: Futile recanalization, defined as lack of clinical benefit despite angiographic recanalization, is an important limitation of endovascular treatment for acute ischemic stroke (AIS). Data on this topic in nonagenarians, who are increasingly being admitted to our hospitals, is scarce. Material & Methods: Retrospective observational study with data collection from