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Walter et al. Vessel Plus 2021;5:27  https://dx.doi.org/10.20517/2574-1209.2020.102                                                                                     Page 7 of 10


                              Table 1. Novel stroke diagnostic tools for stroke diagnosis in the hyperacute phase

                              Device                    Mode of action/aim           Evidence                                                                  Pro/Cons            Ref.

                              Lightweight CT scanner    - Non-thermionic nanotube    - No clinical data available                                              - Detection of other   [38]
                                                        technology                                                                                             brain diseases
                                                        - Differentiation of ischaemic vs.                                                                     possible
                                                        haemorrhagic stroke vs. stroke                                                                         - May be able to
                                                        mimic                                                                                                  include perfusion
                                                                                                                                                               imaging
                                                                                                                                                               - Possibly more
                                                                                                                                                               expensive
                              Microwave technique       - Detects dielectric contrast   - Early clinical studies: area under the curve of 0.85-0.88            - Identification of   [37]
                                                        between tissues (in stroke:   - Phase II/III trial: “Mobile Microwave-based Diagnosis and Monitoring of Stroke: on   stroke mimicking   MODS trial: ClinicalTrials.gov
                                                        contrast between blood and   the Road Towards Improved Stroke Triage and Care, Including Prehospital Initiation of  diseases not possible  Identifier: NCT04257149
                                                        grey and white matter)       Thrombolytic Treatment,” currently recruiting, completion expected Feb 2022  - Low cost
                                                        - Differentiation of ischaemic vs.                                                                     - No perfusion
                                                        haemorrhagic stroke                                                                                    imaging
                              Mobile transcranial       - Ultrasound detection of    - Sensitivity of 78% and specificity of 98%                               - No stand-alone    [40-41]
                              ultrasound including robotics  occlusion signal                                                                                  diagnostic tool
                              and artificial intelligence  - Differentiation of large vessel
                                                        occlusion ischaemic stroke
                              Blood biomarker: glial    - Blood point of care test   - First results STROKECheck device (GFAP, RBP-4, NT-proBNP), Bio-FAST trial): 84%  - Accuracy in early   [42]
                              fibrillary acidic protein   - Differentiation of ischaemic vs.   of ischaemic stroke patients could be identified                hours after symptom   Bio-FAST trial: ClinicalTrials.gov
                              (GFAP), retinol binding   haemorrhagic stroke (vs. stroke                                                                        onset unclear       Identifier: NCT04612218
                              protein (RBP-4) and NT-   mimic)
                                     4                                               - GFAP: meta-analysis (1297 participants) with sensitivity of 0.756 (95%CI: 0.630-            [43]
                              proBNP
                                                                                     0.849), specificity of 0.945 (95%CI: 0.858-0.980), and subgroup time from symptom
                                                                                     onset to GFAP measurement of 0-60 (235 participants); sensitivity ranges from 0.00
                                                                                     (95%CI: 0.00-0.97) to 0.89 (95%CI: 0.65-0.99), and specificity from 0.94 (95%CI:
                                                                                     0.83-0.99) to 1.00 (95%CI: 0.83-1.00)

                                                                                     - GFAP + RBP-4: patients with ICH who had RBP4 < 48.75 microg/mL and GFAP >                   [44]
                                                                                     0.07 ng/mL: sensitivity = 32%, specificity = 100%
                                                                                     - Open label non-randomised, prospective, pre-hospital trial: “Prehospital Advanced           Treat-NASPP: ClinicalTrials.gov
                                                                                     Diagnostics and Treatment of Acute Stroke” to define cut-off values for GFAP and              Identifier:
                                                                                     RBP4                                                                                          NCT03158259Formularende


                              MODS: Mobile Microwave-based Diagnosis and Monitoring of Stroke: on the Road Towards Improved Stroke Triage and Care, Including Prehospital Initiation of Thrombolytic Treatment; GFAP: glial fibrillary acidic
                              protein; RBP-4: retinol binding protein; NT-proBNP: N-terminal pro B-type natriuretic peptide; Treat-NASPP: Prehospital Advanced Diagnostics and Treatment of Acute Stroke.



                              If alternative therapeutic devices shall find a place in acute stroke diagnosis in future, it is likely that several different technologies will need to be combined to

                              allow a more precise diagnosis. However, all of these devices are likely to be small and light enough to be easily transported to acute stroke patients in rural and
                              remote areas, enabling faster diagnosis and timely initiation of treatment.
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