1. Radiology Training Course

2. Timing of Imaging Studies

3. SCREENING AND ELIGIBILITY Pre-Randomization

4. Screening – Diagnostic CT Diagnostic CT (dCT): First CT scan performed diagnosing ICH Used to determine eligibility – Check for Inclusion Criteria Symptom onset <24hrs prior to dCT Spontaneous ICH > 30cc (ABC/2) – Check for Exclusion Criteria

5. Screening – Determining ICH Size with ABC/2 1.Choose the slice for the A and B measurements. 2.Measure the longest diameter possible. This is your A measurement. 3.Measure the longest remaining diameter that is perpendicular to your A measurement line. This is your B measurement. 4.Beginning at the base slice, count the number of slices in which the ICH is visible. Multiply this number by the slice thickness in centimeters. This is your C measurement. For the purpose of determination of (C) diameter, the first and last slices where hematoma is first and last noted are not counted. 5.Multiply A x B x C, and then divide the product by 2. This is your ICH volume in mL (cc). A A’

6. MIII Exclusion Criteria Infratentorial Hemorrhage Obvious extension outside of the 4 th ventricle More subtle cerebellar involvement, could be mistaken as enlarged 4 th ventricle

7. MIII Exclusion Criteria Intraventricular hemorrhage requiring treatment with EVD for IVH mass effect EVD to treat ICP is allowed

8. Screening – Rule out Underlying Pathology MRI (T1, T2, DWI, and GRE) and MRA performed to rule out underlying cerebrovascular or brain pathology CT angiogram or routine angiogram with evaluation for “spot sign” is encouraged and considered SOC to complete the evaluation for aneurysm, AVM, or other malformations.

9. Arteriovenous Malformation 1 51 year old female with suspicious CTA with asymmetric vessels and no clear nidus, so angiogram done revealing an AVM Right lenticulostriate AVM with early draining vein and intra-nidal aneurysm Excluded

10. Arteriovenous Malformation 2 26 year old, underwent MRI/MRA that did not reveal a definite lesion Catheter angiogram done in view of high likelihood of etiology in young patient Angiogram confirmed small thalamic AVM and treated with embolization. Excluded

11. Moyamoya 39 year old with hx of cocaine use enrolled without a CTA or other etiologic screen* CTA done after enrollment, and dosing, demonstrated basal arterial occlusions and Moyamoya collaterals Catheter angiogram confirmed diffuse Moyamoya and associated aneurysms. * A protocol deviation

12. ACom Aneurysm 34 year old patient with ICH and IVH, some basal subarachnoid extension Confirmed ACom aneurysm by angiogram and treated with coiling

13. Screening – Stability CT Stability CT (sCT): at least 6hrs after dCT Used to determine clot stability – ICH must not increase from the Dx CT by > 5mL (as measured by ABC/2) – If clot volume increases by > 5mL, second stability CT must be done 12hrs later

14. ICH Increase Dx CT to Stability CT Diagnostic CT May 2 at 9:46am ICH = 27.03cc Stability CT May 2 at 12:50pm ICH = 58.94cc

15. SURGICAL PLANNING Pre-Randomization

16. Screening – Optimal Trajectory Determination Neurosurgeon will review a 3D reconstruction of ICH on CT to determine optimal burr hole location, catheter trajectory, and hematoma target

17. Upload to EDC: Screen shot showing 3D images and plan for catheter placement (JPEG) Full set of DICOM images for surgical center review and volumetrics on ICH

18. SURGICAL PROCEDURE Randomization MIS + tPA Standard of Care

19. Post-Surgery CT CT scan acquired post- surgery to confirm placement – use windowing to view catheter side ports – measure clot size reduction as compared to the stability CT scan using ABC/2 – If post-surgery clot volume is 10mL, do not administer rt- PA (study endpoint is reached)

20. Post-Surgery CT UPLOAD this CT for Surgical Center review prior to rt-PA administration – Surgical Center review is repeated after any catheter adjustment or replacement 3 hour post surgical stabilization period is required prior to first injection of rt-PA.

21. DAYS 1-4 Dosing & Medical Management

22. Acute Treatment –CTs Days 1-4 Check every CT for: Stability – Check for hemorrhage stability 1.no expansion of ICH > 5 mL as compared to the most previous CT scan 2.no catheter tract bleed > 5mm 3.no new IVH or new expansion of IVH – Check if catheter side ports are still in contact with clot

23. HOLD DOSE Catheter Tract Bleeding >5mm July 29 at 11:30am ICH = 61.57cc

24. HOLD DOSE ICH increase >5mL July 29 at 6:06am ICH = 39.76cc July 29 at 11:30am ICH = 61.57cc

25. HOLD DOSE IVH increase, or new IVH CT 1 IVH = 9.22cc CT 2 IVH = 18.51cc More blood in 4 th ventricle New blood in posterior tip of right lateral ventricle New blood in right lateral ventricle

26. Acute Treatment –CTs Days 1-4 Check every CT for: Treatment Success Endpoints – 80% clot reduction (ABC/2) OR – 10-15 mL of clot remaining Stop dosing if maximum dosage has been administered (9 doses)

27. STOP DOSE – Treatment Success ICH <15mL Stability CT on April 22 ICH = 55.43cc CT on April 26 at 20:47 ICH = 8.26cc Last dose administered April 26 at 17:51

28. END OF TREATMENT

29. End of Treatment Imaging Studies A CT scan must be done 24hrs after the catheter is removed to monitor for new bleeding or bleeding extension Day 7 MRI

30. FOLLOW UP

31. Follow-Up Imaging CT scan required on Day 30 and Day 180 visits Diagnostic CTDay 30 CTDay 365 CT

32. Thanks! - MISTIE III Reading Center