When Can an Emergency CTA Be Dispensed with for TIA Patients?

BACKGROUND: Transient ischemic attacks (TIAs) and minor strokes are often precursors of a major stroke. Therefore, diagnostic work-up of the TIA is essential to reduce the patient's risk of further ischemic events. PURPOSE: With the help of this retrospective study, we aim to determine for which TIA patients a CT angiography (CTA) is not immediately necessary in order to reduce radiation exposure and nephrotoxicity. MATERIAL AND METHODS: Clinical and imaging data from patients who presented as an emergency case with a suspected diagnosis of TIA at a teaching hospital between January 2016 and December 2021 were evaluated. The included 1526 patients were divided into two groups-group 1, with major pathologic vascular findings in the CTA, and group 2, with minor vascular pathologies. RESULTS: Out of 1821 patients with suspected TIA on admission, 1526 met the inclusion criteria. In total, 336 (22%) had major vascular pathologies on CTA, and 1190 (78%) were unremarkable. The majority of patients with major vascular pathologies were male and had a history of arterial hypertension, coronary heart disease, myocardial infarction, ischemic stroke, TIA, atherosclerotic peripheral vascular disease, smoking, antiplatelet medication, had a lower duration of TIA symptoms, and had lower ABCD2 scores. CONCLUSIONS: We were able to demonstrate a direct correlation between major CTA pathologies and a history of smoking, age, hyperlipidemia, history of peripheral arterial disease, and a history of stroke and TIA. We were able to prove that the ABCD2 score is even reciprocal to CTA pathology. This means that TIA patients without described risk factors do not immediately require a CTA and could be clarified in the course of treatment with ultrasound or MRI.

CT and DSA for evaluation of spontaneous intracerebral lobar bleedings.

Purpose: This study retrospectively examined the extent to which computed tomography angiography (CTA) and digital subtraction angiography (DSA) can help identify the cause of lobar intracerebral bleeding. Materials and methods: In the period from 2002 to 2020, data from patients who were >18 years at a university and an academic teaching hospital with lobar intracerebral bleeding were evaluated retrospectively. The CTA DSA data were reviewed separately by two neuroradiologists, and differences in opinion were resolved by consensus after discussion. A positive finding was defined as an underlying vascular etiology of lobar bleeding. Results: The data of 412 patients were retrospectively investigated. DSA detected a macrovascular cause of bleeding in 125/412 patients (33%). In total, sixty patients had AVMs (15%), 30 patients with aneurysms (7%), 12 patients with vasculitis (3%), and 23 patients with dural fistulas (6%). The sensitivity, specificity, positive and negative predictive values, and accuracy of CTA compared with DSA were 93, 97, 100, and 97%. There were false-negative CTA readings for two AVMs and one dural fistula. Conclusion: The DSA is still the gold standard diagnostic modality for detecting macrovascular causes of ICH; however, most patients with lobar ICH can be investigated first with CTA, and the cause of bleeding can be found. Our results showed higher sensitivity and specificity than those of other CTA studies.

Ultrasound Perfusion Imaging for the Detection of Cerebral Hypoperfusion After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral ischemia increases mortality and morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Various techniques are applied to detect cerebral vasospasm and hypoperfusion. Contrast-enhanced ultrasound perfusion imaging (UPI) is able to detect cerebral hypoperfusion in acute ischemic stroke. This prospective study aimed to evaluate the use of UPI to enable detection of cerebral hypoperfusion after aSAH. METHODS: We prospectively enrolled patients with aSAH and performed UPI examinations every second day after aneurysm closure. Perfusion of the basal ganglia was outlined to normalize the perfusion records of the anterior and posterior middle cerebral artery territory. We applied various models to characterize longitudinal perfusion alterations in patients with delayed ischemic neurologic deficit (DIND) across the cohort and predict DIND by using a multilayer classification model. RESULTS: Between August 2013 and December 2015, we included 30 patients into this prospective study. The left-right difference of time to peak (TTP) values showed a significant increase at day 10-12. Patients with DIND demonstrated a significant, 4.86 times increase of the left-right TTP ratio compared with a mean fold change in patients without DIND of 0.9 times (p = 0.032). CONCLUSIONS: UPI is feasible to enable detection of cerebral tissue hypoperfusion after aSAH, and the left-right difference of TTP values is the most indicative result of this finding.

A full year of the COVID-19 pandemic with two infection waves and its impact on ischemic stroke patient care in Germany.

BACKGROUND AND PURPOSE: Many countries worldwide, including Germany, reported that the first wave of the coronavirus disease 2019 (COVID-19) pandemic in early 2020 influenced the care of acute ischemic stroke (AIS) patients, but data are lacking for further pandemic wave periods. METHODS: We conducted a nationwide, retrospective, cross-sectional study of all hospitalized patients with the main diagnosis of AIS in 2019 and 2020. Primary outcomes were the number of hospitalizations for AIS, the application of stroke unit care, intravenous thrombolysis (IVT), and mechanical thrombectomy (MT), as well as the in-hospital mortality during the different pandemic periods in 2020 compared to the corresponding periods in 2019. Secondarily, we analyzed differences in outcomes between patients with and without concurrent COVID-19. RESULTS: We included 429,841 cases with AIS, of which 1268 had concurrent COVID-19. Hospitalizations for AIS declined during both pandemic wave periods in 2020 (first wave: -10.9%, second wave: -4.6%). MT rates were consistently higher throughout 2020 compared to 2019, whereas the IVT rate dropped during the second wave period (16.0% vs. 17.0%, p < 0.001). AIS patients with concurrent COVID-19 frequently received recanalization treatments, with an overall MT rate of 8.4% and IVT rate of 15.9%. The in-hospital mortality was high (22.8% vs. 7.5% in noninfected AIS patients, p < 0.001). CONCLUSIONS: These findings demonstrate a smaller decline in hospitalizations for AIS in the more severe second wave of the COVID-19 pandemic. AIS patients with and without concurrent COVID-19 who did seek acute care continued to receive recanalization treatments in Germany.

The level of urbanization influences acute ischemic stroke care: A nationwide ecological study from Germany.

BACKGROUND AND PURPOSE: Regional differences in acute ischemic stroke (AIS) care are still reported for Germany but not fully understood. We aimed to analyze the impact of the level of urbanization on the application of proved treatment procedures and the incidence of hospitalized AIS cases in Germany. METHODS: The level of urbanization of the 401 districts and district-free cities in Germany was defined according to the Federal Institute for Building, Urban Affairs and Spatial Research classification. Using nationwide administrative data, the application of intravenous thrombolysis (IVT), mechanical thrombectomy (MT), and the incidence of hospitalizations for AIS, were analyzed according to the place of residence of the patients. Data included all patients hospitalized for AIS in 2019 (n = 224,274) and sociodemographic information of 83,019,213 residents in Germany. RESULTS: Sparsely populated districts had a significantly higher incidence of hospitalizations for AIS than cities (age-standardized: 271.8 versus 242.3 per 100,000 inhabitants, P < 0.001), but a lower use of MT (5.7% versus 8.4%, P < 0.001). In the adjusted negative binomial regression model, rurality remained an independent predictor for MT use and the incidence of AIS hospitalizations. The proportion of IVT did not significantly differ between sparsely populated districts and cities (15.6% versus 17.2%, P = 0.021). CONCLUSIONS: Although there is a dense network of stroke units in Germany, the level of urbanization still influences AIS care, as we found a lower proportion of MT and a higher incidence of AIS hospitalizations in Germany's rural areas.

Letter to the Editor: Analysis of stroke patient migration for mechanical thrombectomy and changes in neurointerventional center size in Germany.

AIM AND METHODS: To analyse nationwide changes in neurointerventional center size of all German hospitals performing mechanical thrombectomy (MT) in stroke patients from 2016 to 2019. Furthermore, we assessed cross-district patient migration for MT for the first time using hospitals' structured quality reports and German Diagnosis-Related Groups data in 2019. FINDINGS: Number of hospitals performing more than 100 MT procedures/year doubled in Germany from 2016 (n = 36) to 2019 (n = 71), and these neurointerventional centers performed 71% of all MT procedures in 2019. The overall increase in MT procedures was largely driven by these high-volume neurointerventional centers with ability to perform MT 24/7 (121% increase as compared with 8% increase in hospitals performing less than 100 MT procedures/year). The highest cross-district patient mobility/transfer of stroke patients for MT was observed in districts adjacent to these high-volume neurointerventional centers with existing neurovascular networks. CONCLUSION: The substantial increase in MT procedures observed in Germany between 2016 and 2019 was almost exclusively delivered by high-volume stroke centers performing more than 100 MT procedures per year in established neurovascular networks. As there is still a reasonable number of districts with low MT rates, further structural improvement including implementation of new or expansion of existing neurovascular networks and regional tailored MT triage concepts is needed.

Acute ischemic stroke care in Germany - further progress from 2016 to 2019.

BACKGROUND: Stroke Unit Care (SUC), intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatment options for acute ischemic stroke (AIS). Using nationwide comprehensive administrative data from Germany, we recently reported nationwide development of AIS admissions, SUC rates, IVT rates and MT rates in Germany between 2010 and 2016. In this update paper, we analyze data on the further development of these data to 2019 after publication of time window extensions for recanalization therapies. METHODS: We considered all hospitalized cases with the main diagnosis of the ICD-10-GM code I63 (AIS) for the year 2019. We identified stroke therapies by using the corresponding Operating and Procedure Keys for IVT, MT and SUC out of the DRG statistics. Regional analyses are based on data from the 412 German administrative districts and cities. We compared the results with those from 2016. RESULTS: Number of hospitalized AIS patients showed a mild decrease in 2019 (n = 225,531) compared with 2016 (n = 227,687), with significant more AIS patients treated on a stroke unit in 2019 (n = 167,799; 74.4% vs. n = 164,270; 72.1%, p < 0.001). The rate of IVT further increased from 14.9% (n = 33,916) in 2016 to 16.3% (n = 36,745) in 2019 (p < 0.001). Similarly, the MT rate increased from 4.3% (n = 9795) in 2016 to 7.2% (n = 16,135) in 2019 (p < 0.001). There was still a high regional variability for MT (1.4 to 15.2%) according to the place of residence of the AIS patients. CONCLUSIONS: In Germany, the rates of recanalization therapies in patients with AIS continued to increase from 2016 to 2019. Compared to IVT-rates and numbers, the respective data for MT procedures showed an even more pronounced increase.

Analysis of Nationwide Stroke Patient Care in Times of COVID-19 Pandemic in Germany.

BACKGROUND AND PURPOSE: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many countries have introduced strict hygiene measures of social distancing to prevent further spreading of the disease. This may have led to a decreased presentation to hospital of patients with acute medical conditions and time-dependent management, such as stroke. METHODS: We conducted a nationwide cohort study using administrative database of all hospitalized patients with main diagnosis of acute ischemic stroke (AIS), transient ischemic attack, or intracerebral hemorrhage. Data from a total of 1463 hospitals in Germany were included. We compared case numbers and treatment characteristics of pandemic (March 16 to May 15, 2020) and prepandemic (January 16 to March 15, 2020) cases and also with corresponding time period in 2019. RESULTS: We identified a strong decline for hospitalization of AIS (-17.4%), transient ischemic attack (-22.9%), and intracerebral hemorrhage (-15.8%) patients during the pandemic compared with prepandemic period. IVT rate in patients with AIS was comparable (prepandemic versus pandemic: 16.4% versus 16.6%, P=0.448), whereas mechanical thrombectomy rate was significantly higher during the pandemic (8.1% versus 7.7%, P=0.044). In-hospital mortality was significantly increased in patients with AIS during the pandemic period (8.1% versus 7.6%, P=0.006). CONCLUSIONS: Besides a massive decrease in absolute case numbers, our data suggest that patients with AIS who did seek acute care during the pandemic, continued to receive acute recanalization treatment in Germany.

Comparison of stroke care parameters in acute ischemic stroke patients with and without concurrent Covid-19. A Nationwide analysis.

BACKGROUND: Comparing health care parameters of acute ischemic stroke (AIS) patients with and without concurrent coronavirus disease 2019 (Covid-19, SARS-CoV-2 infection), may be helpful in terms of optimizing clinical and public health care during pandemic. METHODS: We evaluated a nationwide administrative database of all hospitalized patients with main diagnosis of acute ischemic stroke with/without diagnosis of Covid-19 who were hospitalized during the time period from January 16th to May 15th, 2020. Data from a total of 1463 hospitals in Germany were included. We compared case numbers, treatment characteristics (intravenous thrombolysis, IVT; mechanical thrombectomy, MT; treated on an intensive care unit, stroke unit or regular ward) and in-hospital mortality of AIS with and without concurrent diagnosis of Covid-19. RESULTS: From a total of 30,864 hospitalized Covid-19 patients during the evaluation period in Germany, we identified a subgroup of 213 patients with primary diagnosis of AIS. Compared to the 68,700 AIS patients without Covid-19, this subgroup showed a similar rate of IVT (16.4% vs. 16.5%, p = 0.985) but a significantly lower rate of MT (3.8% vs. 7.9%, p = 0.017). In-hospital mortality rate was significantly higher in patients with AIS and concurrent Covid-19 compared to non-infected AIS patients (22.5% vs. 7.8%, p < 0.001). CONCLUSION: These nationwide data point out differences in mortality and medical treatment regime between AIS patients with and without concurrent Covid-19. Since the pandemic is still ongoing, these data draw attention to AIS as a less frequent but often fatal comorbidity in Covid-19 patients.

Twenty Years of Cerebral Ultrasound Perfusion Imaging-Is the Best yet to Come?

Over the past 20 years, ultrasonic cerebral perfusion imaging (UPI) has been introduced and validated applying different data acquisition and processing approaches. Clinical data were collected mainly in acute stroke patients. Some efforts were undertaken in order to compare different technical settings and validate results to gold standard perfusion imaging. This review illustrates the evolution of the method, explicating different technical aspects and milestones achieved over time. Up to date, advancements of ultrasound technology as well as data processing approaches enable semi-quantitative, gold standard proven identification of critically hypo-perfused tissue in acute stroke patients. The rapid distribution of CT perfusion over the past 10 years has limited the clinical need for UPI. However, the unexcelled advantage of mobile application raises reasonable expectations for future applications. Since the identification of intracerebral hematoma and large vessel occlusion can also be revealed by ultrasound exams, UPI is a supplementary multi-modal imaging technique with the potential of pre-hospital application. Some further applications are outlined to highlight the future potential of this underrated bedside method of microcirculatory perfusion assessment.

Age and Sex Differences in Ischemic Stroke Treatment in a Nationwide Analysis of 1.11 Million Hospitalized Cases.

Background and Purpose- To date, there is still uncertainty about age and sex differences in access to stroke unit treatment and use of intravenous thrombolysis (IVT), while age and sex differences have not been investigated for the new treatment option of mechanical thrombectomy (MT). We, therefore, undertook a complete nationwide analysis of all hospitalized ischemic stroke patients in Germany from 2013 to 2017. Methods- We used the nationwide administrative database of the German Federal Statistical Office and investigated access to stroke unit treatment, IVT, MT, and in-hospital mortality. Patients were subdivided into 6 predefined age groups (20-44, 45-59, 60-69, 70-79, 80-89, and >90 years). Pooled overall and age group estimates were calculated using the random-effects model. To evaluate potential sex disparities, we estimated odds ratios (ORs) with 95% CIs. Results- A total of 1 112 570 patients were hospitalized for first or recurrent ischemic stroke from 2013 to 2017. Overall, stroke unit treatment increased significantly from 66.8% in 2013 to 73.5% in 2017, as did IVT (from 12.4% to 15.9%) and MT (from 2.4% to 5.8%; all P<0.001). Although the difference became smaller over time, patients ≥80 years of age still received significantly less often treatments. Men of all age groups had a significantly higher probability receiving stroke unit treatment (OR, 1.11; 95% CI, 1.09-1.12) and lower in-hospital mortality (OR, 0.91; 95% CI, 0.89-0.93). No disparity was observed in the use of IVT (OR, 1.00; 95% CI, 0.98-1.01), while women of all ages were treated more often with MT (OR, 1.26; 95% CI, 1.22-1.30). Conclusions- Access to stroke unit treatment has to be increased in both older patients and women of all ages. While there was no sex difference in IVT use, it is important to further investigate the significantly higher frequency of MT in women with ischemic stroke irrespective of age.

Ultrasonic quantification of cerebral perfusion in acute anterior circulation occlusive stroke-A comparative challenge of the refill- and the bolus-kinetics approach.

PURPOSE: To prospectively evaluate the potential of semi-quantitative evaluation of cerebral perfusion in acute ischemic stroke by comparing two established ultrasound approaches. MATERIALS AND METHODS: Consecutive inclusion of patients with acute occlusion of middle cerebral artery (MCA) confirmed by either magnetic resonance imaging (MRI) or computed tomography (CT) perfusion imaging qualifying for interventional therapy. Comparison of bilateral high mechanical index (MI) bolus-kinetics (HighMiB) and unilateral low MI refill-kinetics (LowMiR) performed before specific treatment. RESULTS: In 16/31 patients HighMiB was eligible, in 8/31 patients LowMiR was eligible. In six out of these eight patients both HighMiB and LowMiR were eligible for direct comparison. In MR/CT perfusion imaging of the 16 patients eligible for HighMiB, 29/48 cortical regions of interest (ROIs) (60%) displayed hypoperfusion or ischemia, areas inadequately accessible by LowMiR. These ROIs made up 49% of the 59 ROIs displaying hypoperfusion or ischemia, altogether. Matching of parameters in normal and impaired ROIs between LowMiR and MRI/CT perfusion imaging was significantly poorer than in HighMiB. CONCLUSION: LowMiR using refill-kinetics potentially has the advantage of real time imaging and better resolution. The diagnostic impact, however, proves inferior to HighMiB both with respect to imaging quality and semi-quantitative evaluation.

Distribution and evolution of acute interventional ischemic stroke treatment in Germany from 2010 to 2016.

BACKGROUND: Mechanical thrombectomy (MT) is a new evidence-based treatment option for large vessel occlusion in the anterior brain circulation. Using comprehensive administrative data from Germany, we analysed the nationwide development of intravenous thrombolysis (IVT) and MT in Germany between 2010 and 2016. METHODS: We considered all documented cases (n = 1,515,634) with a main diagnosis of the ICD-10-GM code I63 (ischemic stroke) and identified specific stroke recanalization therapy by using the corresponding Operating and Procedure Key for systemic thrombolysis and mechanical thrombectomy out of the DRG statistics. Regional analyses are based on data from the 413 German administrative districts and cities and the obligatory quality reports of all hospitals. We distinguished between rates of MT related to place of residence of patients and place of treatment. RESULTS: Coded ischemic strokes increased by 10.2% from 2010 (n = 206.688) to 2016 (n = 227.687). The rate of IVT increased from 8.9% in 2010 to 14.9% in 2016 and the rate of MT increased from 0.8% in 2010 to 4.7% in 2016 with a strong increase in 2015 and 2016. There was a high regional variability of MT according to place of residence of patients between 0 and 11.2% in 2016 with significant lower treatment rates in rural compared to urban areas (3.8 vs 5.4%). Mean age of patients treated with MT increased from 67.8 years in 2010 to 73.3 years in 2016 and almost reached the mean age of IVT treated patients (74.4 years). The number of hospitals coding MT increased from 91 to 193 from 2010 to 2016, but 80% of all MT procedures were performed in neurointerventional centers with ≥50 procedures/year in 2016. CONCLUSIONS: The rate of IVT in patients with acute ischemic stroke in Germany continues to rise and has reached 14.9% nationwide. The increase of MT is even more pronounced and was triggered by the evidence after publication of the MT randomized trials. There is still a high regional variability with significant lower MT rates in rural areas.

Inpatient TIA and stroke care in adult patients in Germany - retrospective analysis of nationwide administrative data sets of 2011 to 2017.

BACKGROUND: Comprehensive administrative data on TIA and stroke cases and treatment modalities are fundamental for improving structural conditions and adjusting future strategies of stroke care. METHODS: The nationwide administrative database (German federal statistical office) was used to extract all adult inpatient TIA and stroke cases and corresponding procedural codes for the period 2011-2017. Numbers were specified according to age, sex, stroke unit (SU) and critical care treatment (ICU), early transfer, and in-hospital mortality. FINDINGS: Inpatient adult TIA/stroke cases increased from annually 102,406 / 250,199 (2011) to 106,245 / 264,208 (2017). 84% of strokes were ischemic (AIS) also having the highest relative increase most likely due to more accurate coding within the time period, 68.2% of AIS were treated on SUs. 78% of hemorrhagic strokes were intracerebral hematomas (ICH; rather than subarachnoid hemorrhages [SAH]). Hemorrhagic strokes were increasingly treated on SUs (32.6% [2011], 37.8% [2017]). 68.8% of SAH were treated on ICUs (ICH:36.3%, AIS:10.3%). Early transfer in AIS increased (2.0 to 3.1%). Hemorrhagic strokes were associated with higher in-hospital mortality (SAH:19.6%, ICH:28.2%, AIS:7.3%). INTERPRETATION: The absolute increase of strokes presumably reflects the aging society and more awareness for cerebrovascular disease. The relative increase of AIS may be attributable to an increased neurological expertise. The increasing amount of early transfers in AIS reflects new specialized treatment options. Our findings reflect the need for structural adjustments in inpatient stroke care.

Stroke admission outside daytime working hours delays mechanical thrombectomy and worsens short-term outcome.

BACKGROUND AND PURPOSE: Rapid therapeutic decisions in acute stroke patients leading to earlier initiation of revascularization therapies are associated with better outcome. An association between regular working hours and reduced time to initiation of intravenous thrombolysis has been reported. However, its influence on mechanical thrombectomy (MT) remains uncertain. We aimed to analyze the effects of admission time on door-to-groin time and stroke outcome in a large prospective stroke registry of the Neurovascular Net Ruhr in Germany. METHODS: Procedural times of a total of 512 patients treated with MT were analyzed. Admission to hospital during regular working days and hours (Monday to Friday, 8 am to 4 pm) was compared with admission outside these times. Door-to-groin time and the difference in NIH Stroke Scale between admission and discharge served as primary outcome parameters. Long-term functional outcome was centrally assessed with modified Rankin scale. RESULTS: MT outside regular working hours was associated with a significant mean initiation delay of 20 min. By multivariate regression analysis, every 20 min delay of MT reduced the difference in NIHSS score between admission and discharge by 0.76 points (95% CI -1.24 to -0.28, p = 0.002). Favorable long-term outcome did not differ between both treatment groups. CONCLUSIONS: Treatment outside regular working hours caused a significant delay in the initiation of MT, which was associated with a decreased short-term clinical efficacy of thrombectomy. Strategies like compulsory attendance of the interventional neuroradiologist at the hospital 24/7 might result in shorter door-to-groin times and consecutive in better stroke outcome.

Quantification of Macrocirculation and Microcirculation in Brain Using Ultrasound Perfusion Imaging.

OBJECTIVE: The aim of this study was to investigate the feasibility of simultaneous visualization of the cerebral macrocirculation and microcirculation, using ultrasound perfusion imaging (UPI). In addition, we studied the sensitivity of this technique for detecting changes in cerebral blood flow (CBF). MATERIALS AND METHODS: We performed an observational study in ten healthy volunteers. Ultrasound contrast was used for UPI measurements during normoventilation and hyperventilation. For the data analysis of the UPI measurements, an in-house algorithm was used to visualize the DICOM files, calculate parameter images and select regions of interest (ROIs). Next, time intensity curves (TIC) were extracted and perfusion parameters calculated. RESULTS: Both volume- and velocity-related perfusion parameters were significantly different between the macrocirculation and the parenchymal areas. Hyperventilation-induced decreases in CBF were detectable by UPI in both the macrocirculation and microcirculation, most consistently by the volume-related parameters. The method was safe, with no adverse effects in our population. CONCLUSIONS: Bedside quantification of CBF seems feasible and the technique has a favourable safety profile. Adjustment of current method is required to improve its diagnostic accuracy. Validation studies using a 'gold standard' are needed to determine the added value of UPI in neurocritical care monitoring.

Repeatability of Bolus Kinetics Ultrasound Perfusion Imaging for the Quantification of Cerebral Blood Flow.

Ultrasound perfusion imaging (UPI) can be used for the quantification of cerebral perfusion. In a neuro-intensive care setting, repeated measurements are required to evaluate changes in cerebral perfusion and monitor therapy. The aim of this study was to determine the repeatability of UPI in quantification of cerebral perfusion. UPI measurement of cerebral perfusion was performed three times in healthy patients. The coefficients of variation of the three bolus injections were calculated for both time- and volume-derived perfusion parameters in the macro- and microcirculation. The UPI time-dependent parameters had overall the lowest CVs in both the macro- and microcirculation. The volume-related parameters had poorer repeatability, especially in the microcirculation. Both intra-observer variability and inter-observer variability were low. Although UPI is a promising tool for the bedside measurement of cerebral perfusion, improvement of the technique is required before implementation in routine clinical practice.