Clinical studies with transcranial Doppler suggest that the pulsatility of the flow velocity (FV) waveform increases when the distal cerebrovascular resistance (CVR) increases. To clarify this relationship, the authors studied animal models in which the resistance may be decreased in a controlled manner by an increase in arterial CO2 tension, or by a decrease in cerebral perfusion pressure (CPP) in autoregulating animals. Twelve New Zealand white rabbits were anesthetized, paralyzed, and ventilated. Transcranial Doppler basilar artery FV, laser Doppler cortical blood flow, arterial pressure, intracranial pressure, and end-tidal CO2 concentration were measured continuously. Cerebrovascular resistance (CPP divided by laser Doppler cortical flux) and Gosling Pulsatility Index (PI, defined as an FV pulse amplitude divided by a timed average FV) were calculated as time-dependent variables for each animal. Four groups of animals undergoing controlled manipulations of CVR were analyzed. In Group I, arterial CO2 concentration was changed gradually from hypocapnia to hypercapnia. In Group II, gradual hemorrhagic hypotension was used to reduce CPP. In Group III, the short-acting ganglion blocking drug trimetaphan was injected intravenously to induce transient hypotension. Intracranial hypertension was produced by subarachnoid saline infusion in Group IV. During the hypercapnic challenge the correlation between the cortical resistance and Doppler flow pulsatility was positive (r = 0.77, p<0.001). In all three groups in which cerebral perfusion pressure was reduced a negative correlation between pulsatility index and cerebrovascular resistance was found (r = -0.84, p<0.001). The authors conclude that PI cannot be interpreted simply as an index of CVR in all circumstances.

The appendix presents an introduction to the mathematical modelling of CSF pressure volume-compensation included in computerised infusion test software.

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The distribution of periventricular edema in acute hydrocephalus is a result not only of increased intraventricular pressure but also of ventricular geometry.

A mathematical model of cerebral blood flow and the cerebrospinal fluid circulation is described which permits the study of phenomena caused by dynamic changes in cerebrovascular autoregulatory or cerebrospinal fluid compensatory reserves. A transient decrease in cerebral perfusion pressure was produced by carotid artery compression. Comparison of the computer simulations with clinical and experimental data, reported elsewhere, suggests that the transient hyperaemic response (THR) is proportional to the strength of the autoregulatory response. The relationships between the magnitude and time course of the THR, and the period and level of reduction in CPP were studied. This model suggests that simple clinical tests based on the examination of THR using transcranial Doppler velocity measurements are of potential value for the non-invasive assessment of the autoregulatory reserve.

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Background Minimal/measurable residual disease (MRD) testing by flow cytometry (FC) has been proposed as a potential surrogate clinical endpoint in plasma cell myeloma (PCM) clinical trials. As a result, effort has gone into standardizing this approach on PCM patients. Aims To assess inter‐laboratory variation in FC MRD testing of PCM patients in an independent inter‐laboratory study. Methods A dilution series of five stabilized bone marrow samples manufactured to contain 0%, 0.1%, 0.01%, 0.001%, and 0.0001% neoplastic plasma cells (PCs) were tested blind, using standardized FC PCM MRD assays by 10 international laboratories. Results Laboratories' assays broadly adhered to the consensus guidelines; however, some deviations were identified in panel design, fluorochrome conjugates, and lysis reagents. Despite this, all laboratories that returned results detected neoplastic PCs down to 0.001% of leucocytes. 6/8 laboratories detected neoplastic PCs at a level of 0.0001%. Quantitative data returned by laboratories showed good consensus and linearity with increasing variation at lower levels of MRD. However, examples of analytical and post analytical error were identified. Summary/Conclusion Broadly standardized PCM MRD FC assays can attain the lower limit of detection (LOD) required by current and future clinical trials, an important consideration in establishing PCM MRD testing as a surrogate clinical marker in PCM clinical trials. Laboratories' assays showed good linearity, encouraging the prediction of survival based on log reduction in neoplastic PC populations in future clinical trials. However, the deviations from consensus guidelines identified in this study would suggest that if PCM MRD assays are further standardized interlaboratory variation could be reduced. © 2018 International Clinical Cytometry Society