Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation

Background: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. Main body: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI. Indeed, evidence suggests that the transient receptor potential cation channels (TRP channels), TRPV1 and TRPA1, are polymodal receptors that are activated by a variety of stimuli associated with TBI, including mechanical shear stress, leading to the release of neuropeptides such as substance P (SP). SP augments many aspects of the classical inflammatory response via activation of microglia and astrocytes, degranulation of mast cells, and promoting leukocyte migration. Furthermore, SP may initiate the earliest changes seen in blood-brain barrier (BBB) permeability, namely the increased transcellular transport of plasma proteins via activation of caveolae. This is in line with reports that alterations in transcellular transport are seen first following TBI, prior to decreases in expression of tight-junction proteins such as claudin-5 and occludin. Indeed, the receptor for SP, the tachykinin NK1 receptor, is found in caveolae and its activation following TBI may allow influx of albumin and other plasma proteins which directly augment the inflammatory response by activating astrocytes and microglia. Conclusions: As such, the neurogenic inflammatory response can exacerbate classical inflammation via a positive feedback loop, with classical inflammatory mediators such as bradykinin and prostaglandins then further stimulating TRP receptors. Accordingly, complete inhibition of neuroinflammation following TBI may require the inhibition of both classical and neurogenic inflammatory pathways.Frances Corrigan, Kimberley A. Mander, Anna V. Leonard and Robert Vin

Does iterative reconstruction lower CT radiation dose: evaluation of 15,000 examinations.

PURPOSE: Evaluation of 15,000 computed tomography (CT) examinations to investigate if iterative reconstruction (IR) reduces sustainably radiation exposure. METHOD AND MATERIALS: Information from 15,000 CT examinations was collected, including all aspects of the exams such as scan parameter, patient information, and reconstruction instructions. The examinations were acquired between January 2010 and December 2012, while after 15 months a first generation IR algorithm was installed. To collect the necessary information from PACS, RIS, MPPS and structured reports a Dose Monitoring System was developed. To harvest all possible information an optical character recognition system was integrated, for example to collect information from the screenshot CT-dose report. The tool transfers all data to a database for further processing such as the calculation of effective dose and organ doses. To evaluate if IR provides a sustainable dose reduction, the effective dose values were statistically analyzed with respect to protocol type, diagnostic indication, and patient population. RESULTS: IR has the potential to reduce radiation dose significantly. Before clinical introduction of IR the average effective dose was 10.1±7.8mSv and with IR 8.9±7.1mSv (p*=0.01). Especially in CTA, with the possibility to use kV reduction protocols, such as in aortic CTAs (before IR: average14.2±7.8mSv; median11.4mSv /with IR:average9.9±7.4mSv; median7.4mSv), or pulmonary CTAs (before IR: average9.7±6.2mSV; median7.7mSv /with IR: average6.4±4.7mSv; median4.8mSv) the dose reduction effect is significant(p*=0.01). On the contrary for unenhanced low-dose scans of the cranial (for example sinuses) the reduction is not significant (before IR:average6.6±5.8mSv; median3.9mSv/with IR:average6.0±3.1mSV; median3.2mSv). CONCLUSION: The dose aspect remains a priority in CT research. Iterative reconstruction algorithms reduce sustainably and significantly radiation dose in the clinical routine. Our results illustrate that not only in studies with a limited number of patients but also in the clinical routine, IRs provide long-term dose saving

Evaluation der intratherapeutischen Dosimetrie bei der 177Lu-HA-DOTATATE Therapie neuroendokriner Tumoren mittels SPECT, Ganzkörperszintigraphie und Gammasonde

Aim Peptide receptor radionuclide therapy (PRRT) with (177) Lu-HA-DOTATATE has evolved as a new path in the treatment of somatostatin-receptor-expressing neuroendocrine tumors. The kidneys are proven as organs at risk and should be evaluated dosimetrically. Overlap with other organs will make dosimetry based on planar scintigraphy inaccurate. Aim of this study was to approximate the contribution of the kidneys to conjugated planar views without the use of a SPECT/CT. Material and Method An algorithm was developed to determine the kidney dose using an EXCEL (Microsoft) based program. Dosimetric data were drawn and merged from three modalities: an individually calibrated gamma probe, a whole-body scintigraphy (WBS) and SPECT-acquisitions. The method was evaluated for 85 kidneys. Kidney masses were obtained via CT volumetry. Results The developed algorithm combines data from the three modalities. The ratio of the events within a kidney-VOI and the events from the summed coronary SPECT views (kidney ROI) represents the contribution of the kidney to the whole-body kidney ROI. This fraction was calculated to 49 % (17 % - 78 %) and 45 % (18 % - 75 %) for the left and the right kidney, respectively. Quantification of activity was deduced from equalizing the WBS count with the concurrent gamma probe measurement. Monoexponential curves were fitted to the obtained kidney activities, with resulting doses of 0,13 to 0,77 Gy/GBq (average 0,36 and 0,39 Gy/GBq for the left and the right kidney). Conclusion The presented method is suitable to perform kidney dosimetry by using a gamma probe and a gamma camera, without using SPECT/CT