Publications by authors named "Adithya S Reddy"

5 Publications

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Failure modes and effects analysis of mechanical thrombectomy for stroke discovered in human brains.

J Neurosurg 2021 Jun 4:1-8. Epub 2021 Jun 4.

3Neurosurgery, University of Michigan, Ann Arbor, Michigan.

Objective: Despite advancement of thrombectomy technologies for large-vessel occlusion (LVO) stroke and increased user experience, complete recanalization rates linger around 50%, and one-third of patients who have undergone successful recanalization still experience poor neurological outcomes. To enhance the understanding of the biomechanics and failure modes, the authors conducted an experimental analysis of the interaction of emboli/artery/devices in the first human brain test platform for LVO stroke described to date.

Methods: In 12 fresh human brains, 105 LVOs were recreated by embolizing engineered emboli analogs and recanalization was attempted using aspiration catheters and/or stent retrievers. The complex mechanical interaction between diverse emboli (elastic, stiff, and fragment prone), arteries (anterior and posterior circulation), and thrombectomy devices were observed, analyzed, and categorized. The authors systematically evaluated the recanalization process through failure modes and effects analysis, and they identified where and how thrombectomy devices fail and the impact of device failure.

Results: The first-pass effect (34%), successful (71%), and complete (60%) recanalization rates in this model were consistent with those in the literature. Failure mode analysis of 184 passes with thrombectomy devices revealed the following. 1) Devices loaded the emboli with tensile forces leading to elongation and intravascular fragmentation. 2) In the presence of anterograde flow, small fragments embolize to the microcirculation and large fragments result in recurrent vessel occlusion. 3) Multiple passes are required due to recurrent (15%) and residual (73%) occlusions, or both (12%). 4) Residual emboli remained in small branching and perforating arteries in cases of alleged complete recanalization (28%). 5) Vacuum caused arterial collapse at physiological pressures (27%). 6) Device withdrawal caused arterial traction (41%), and severe traction provoked avulsion of perforating and small branching arteries.

Conclusions: Biomechanically superior thrombectomy technologies should prevent unrestrained tensional load on emboli, minimize intraluminal embolus fragmentation and release, improve device/embolus integration, recanalize small branching and perforating arteries, prevent arterial collapse, and minimize traction.
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http://dx.doi.org/10.3171/2020.11.JNS203684DOI Listing
June 2021

A human brain test bed for research in large vessel occlusion stroke.

J Neurosurg 2021 Jan 22:1-9. Epub 2021 Jan 22.

1Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan.

Objective: Endovascular removal of emboli causing large vessel occlusion (LVO)-related stroke utilizing suction catheter and/or stent retriever technologies or thrombectomy is a new standard of care. Despite high recanalization rates, 40% of stroke patients still experience poor neurological outcomes as many cases cannot be fully reopened after the first attempt. The development of new endovascular technologies and techniques for mechanical thrombectomy requires more sophisticated testing platforms that overcome the limitations of phantom-based simulators. The authors investigated the use of a hybrid platform for LVO stroke constructed with cadaveric human brains.

Methods: A test bed for embolic occlusion of cerebrovascular arteries and mechanical thrombectomy was developed with cadaveric human brains, a customized hydraulic system to generate physiological flow rate and pressure, and three types of embolus analogs (elastic, stiff, and fragment-prone) engineered to match mechanically and phenotypically the emboli causing LVO strokes. LVO cases were replicated in the anterior and posterior circulation, and thrombectomy was attempted using suction catheters and/or stent retrievers.

Results: The test bed allowed radiation-free visualization of thrombectomy for LVO stroke in real cerebrovascular anatomy and flow conditions by transmural visualization of the intraluminal elements and procedures. The authors were able to successfully replicate 105 LVO cases with 184 passes in 12 brains (51 LVO cases and 82 passes in the anterior circulation, and 54 LVO cases and 102 passes in the posterior circulation). Observed recanalization rates in this model were graded using a Recanalization in LVO (RELVO) scale analogous to other measures of recanalization outcomes in clinical use.

Conclusions: The human brain platform introduced and validated here enables the analysis of artery-embolus-device interaction under physiological hemodynamic conditions within the unmodified complexity of the cerebral vasculature inside the human brain.
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http://dx.doi.org/10.3171/2020.7.JNS202278DOI Listing
January 2021

Standardized Fabrication Method of Human-Derived Emboli with Histologic and Mechanical Quantification for Stroke Research.

J Stroke Cerebrovasc Dis 2020 Nov 7;29(11):105205. Epub 2020 Aug 7.

Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA; Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota, USA. Electronic address:

Background: As access to patient emboli is limited, embolus analogs (EAs) have become critical to the research of large vessel occlusion (LVO) stroke and the development of thrombectomy technology. To date, techniques for fabricating standardized human blood-derived EAs are limited in the variety of compositions, and the mechanical properties relevant to thrombectomy are not quantified.

Methods: EAs were made by mixing human banked red blood cells (RBCs), plasma, and platelet concentrate in 10 different volumetric percentage combinations to mimic the broad range of patient emboli causing LVO strokes. The samples underwent histologic analysis and tensile testing to mimic the pulling action of thrombectomy devices, and were compared to patient emboli.

Results: EAs had histologic compositions of 0-96% RBCs, 0.78%-92% fibrin, and 2.1%-22% platelets, which can be correlated with the ingredients using a regression model. At fracture, EAs elongated from 81% to 136%, and the ultimate tensile stress ranged from 16 to 949 kPa. These EAs' histologic compositions and tensile properties showed great similarity to those of emboli retrieved from LVO stroke patients, indicating the validity of such EA fabrication methods. EAs with lower RBC and higher fibrin contents are more extensible and can withstand higher tensile stress.

Conclusions: EAs fabricated and tested using the proposed new methods provide a platform for stroke research and pre-clinical development of thrombectomy devices.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105205DOI Listing
November 2020

Construction of a comprehensive endovascular test bed for research and device development in mechanical thrombectomy in stroke.

J Neurosurg 2020 Apr 3;134(3):1190-1197. Epub 2020 Apr 3.

Departments of1Neurosurgery and.

Objective: The development of new endovascular technologies and techniques for mechanical thrombectomy in stroke has greatly relied on benchtop simulators. This paper presents an affordable, versatile, and realistic benchtop simulation model for stroke.

Methods: A test bed for embolic occlusion of cerebrovascular arteries and mechanical thrombectomy was developed with 3D-printed and commercially available cerebrovascular phantoms, a customized hydraulic system to generate physiological flow rate and pressure, and 2 types of embolus analogs (elastic and fragment-prone) capable of causing embolic occlusions under physiological flow.

Results: The test bed was highly versatile and allowed realistic, radiation-free mechanical thrombectomy for stroke due to large-vessel occlusion with rapid exchange of geometries and phantom types. Of the transparent cerebrovascular phantoms tested, the 3D-printed phantom was the easiest to manufacture, the glass model offered the best visibility of the interaction between embolus and thrombectomy device, and the flexible model most accurately mimicked the endovascular system during device navigation. None of the phantoms modeled branches smaller than 1 mm or perforating arteries, and none underwent realistic deformation or luminal collapse from device manipulation or vacuum. The hydraulic system created physiological flow rate and pressure leading to iatrogenic embolization during thrombectomy in all phantoms. Embolus analogs with known fabrication technique, structure, and tensile strength were introduced and consistently occluded the middle cerebral artery bifurcation under physiological flow, and their interaction with the device was accurately visualized.

Conclusions: The test bed presented in this study is a low-cost, comprehensive, realistic, and versatile platform that enabled high-quality analysis of embolus-device interaction in multiple cerebrovascular phantoms and embolus analogs.
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http://dx.doi.org/10.3171/2020.1.JNS192732DOI Listing
April 2020

Analysis of human emboli and thrombectomy forces in large-vessel occlusion stroke.

J Neurosurg 2020 Feb 28;134(3):893-901. Epub 2020 Feb 28.

Departments of3Neurosurgery and.

Objective: This study's purpose was to improve understanding of the forces driving the complex mechanical interaction between embolic material and current stroke thrombectomy devices by analyzing the histological composition and strength of emboli retrieved from patients and by evaluating the mechanical forces necessary for retrieval of such emboli in a middle cerebral artery (MCA) bifurcation model.

Methods: Embolus analogs (EAs) were generated and embolized under physiological pressure and flow conditions in a glass tube model of the MCA. The forces involved in EA removal using conventional endovascular techniques were described, analyzed, and categorized. Then, 16 embolic specimens were retrieved from 11 stroke patients with large-vessel occlusions, and the tensile strength and response to stress were measured with a quasi-static uniaxial tensile test using a custom-made platform. Embolus compositions were analyzed and quantified by histology.

Results: Uniaxial tension on the EAs led to deformation, elongation, thinning, fracture, and embolization. Uniaxial tensile testing of patients' emboli revealed similar soft-material behavior, including elongation under tension and differential fracture patterns. At the final fracture of the embolus (or dissociation), the amount of elongation, quantified as strain, ranged from 1.05 to 4.89 (2.41 ± 1.04 [mean ± SD]) and the embolus-generated force, quantified as stress, ranged from 63 to 2396 kPa (569 ± 695 kPa). The ultimate tensile strain of the emboli increased with a higher platelet percentage, and the ultimate tensile stress increased with a higher fibrin percentage and decreased with a higher red blood cell percentage.

Conclusions: Current thrombectomy devices remove emboli mostly by applying linear tensile forces, under which emboli elongate until dissociation. Embolus resistance to dissociation is determined by embolus strength, which significantly correlates with composition and varies within and among patients and within the same thrombus. The dynamic intravascular weakening of emboli during removal may lead to iatrogenic embolization.
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http://dx.doi.org/10.3171/2019.12.JNS192187DOI Listing
February 2020
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