Publications by authors named "Joshua Cockrum"

4 Publications

  • Page 1 of 1

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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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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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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February 2020

Retrieval and clinical analysis of distraction-based dual growing rod constructs for early-onset scoliosis.

Spine J 2017 10 26;17(10):1506-1518. Epub 2017 Apr 26.

US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA; Fischell Department of Bioengineering, University of Maryland, Room 2330, Jeong H. Kim Engineering Building, Bldg #225, College Park, MD 20742, USA.

Background Context: Growing rod constructs are an important contribution for treating patients with early-onset scoliosis. These devices experience high failure rates, including rod fractures.

Purpose: The objective of this study was to identify the failure mechanism of retrieved growing rods, and to identify differences between patients with failed and intact constructs.

Study Design/setting: Growing rod patients who had implant removal and were previously enrolled in a multicenter registry were eligible for this study.

Patient Sample: Forty dual-rod constructs were retrieved from 36 patients across four centers, and 34 of those constructs met the inclusion criteria. Eighteen constructs failed due to rod fracture. Sixteen intact constructs were removed due to final fusion (n=7), implant exchange (n=5), infection (n=2), or implant prominence (n=2).

Outcome Measures: Analyses of clinical registry data, radiographs, and retrievals were the outcome measures.

Methods: Retrievals were analyzed with microscopic imaging (optical and scanning electron microscopy) for areas of mechanical failure, damage, and corrosion. Failure analyses were conducted on the fracture surfaces to identify failure mechanism(s). Statistical analyses were performed to determine significant differences between the failed and intact groups.

Results: The failed rods fractured due to bending fatigue under flexion motion. Construct configuration and loading dictate high bending stresses at three distinct locations along the construct: (1) mid-construct, (2) adjacent to the tandem connector, or (3) adjacent to the distal anchor foundation. In addition, high torques used to insert set screws may create an initiation point for fatigue. Syndromic scoliosis, prior rod fractures, increase in patient weight, and rigid constructs consisting of tandem connectors and multiple crosslinks were associated with failure.

Conclusion: This is the first study to examine retrieved, failed growing rod implants across multiple centers. Our analysis found that rod fractures are due to bending fatigue, and that stress concentrations play an important role in rod fractures. Recommendations are made on surgical techniques, such as the use of torque-limiting wrenches or not exceeding the prescribed torques. Additional recommendations include frequent rod replacement in select patients during scheduled surgeries.
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October 2017