Clinical situations for which 3D Printing is considered an appropriate representation or extension of data contained in a medical imaging examination: vascular conditions.

BACKGROUND: Medical three-dimensional (3D) printing has demonstrated utility and value in anatomic models for vascular conditions. A writing group composed of the Radiological Society of North America (RSNA) Special Interest Group on 3D Printing (3DPSIG) provides appropriateness recommendations for vascular 3D printing indications. METHODS: A structured literature search was conducted to identify all relevant articles using 3D printing technology associated with vascular indications. Each study was vetted by the authors and strength of evidence was assessed according to published appropriateness ratings. RESULTS: Evidence-based recommendations for when 3D printing is appropriate are provided for the following areas: aneurysm, dissection, extremity vascular disease, other arterial diseases, acute venous thromboembolic disease, venous disorders, lymphedema, congenital vascular malformations, vascular trauma, vascular tumors, visceral vasculature for surgical planning, dialysis access, vascular research/development and modeling, and other vasculopathy. Recommendations are provided in accordance with strength of evidence of publications corresponding to each vascular condition combined with expert opinion from members of the 3DPSIG. CONCLUSION: This consensus appropriateness ratings document, created by the members of the 3DPSIG, provides an updated reference for clinical standards of 3D printing for the care of patients with vascular conditions.

Radiological Society of North America (RSNA) 3D Printing Special Interest Group (SIG) clinical situations for which 3D printing is considered an appropriate representation or extension of data contained in a medical imaging examination: breast conditions.

The use of medical 3D printing has expanded dramatically for breast diseases. A writing group composed of the Radiological Society of North America (RSNA) Special Interest Group on 3D Printing (SIG) provides updated appropriateness criteria for breast 3D printing in various clinical scenarios. Evidence-based appropriateness criteria are provided for the following clinical scenarios: benign breast lesions and high-risk breast lesions, breast cancer, breast reconstruction, and breast radiation (treatment planning and radiation delivery).

Investigation of convolutional neural networks using multiple computed tomography perfusion maps to identify infarct core in acute ischemic stroke patients.

Purpose: To assess acute ischemic stroke (AIS) severity, infarct is segmented using computed tomography perfusion (CTP) software, such as RAPID, Sphere, and Vitrea, relying on contralateral hemisphere thresholds. Since this approach is potentially patient dependent, we investigated whether convolutional neural networks (CNNs) could achieve better performances without the need for contralateral hemisphere thresholds. Approach: CTP and diffusion-weighted imaging (DWI) data were retrospectively collected for 63 AIS patients. Cerebral blood flow (CBF), cerebral blood volume (CBV), time-to-peak, mean-transit-time (MTT), and delay time maps were generated using Vitrea CTP software. U-net shaped CNNs were developed, trained, and tested for 26 different input CTP parameter combinations. Infarct labels were segmented from DWI volumes registered with CTP volumes. Infarct volumes were reconstructed from two-dimensional CTP infarct segmentations. To remove erroneous segmentations, conditional random field (CRF) postprocessing was applied and compared with prior results. Spatial and volumetric infarct agreement was assessed between DWI and CTP (CNNs and commercial software) using median infarct difference, median absolute error, dice coefficient, positive predictive value. Results: The most accurate combination of parameters for CNN segmenting infarct using CRF postprocessing was CBF, CBV, and MTT (4.83 mL, 10.14 mL, 0.66, 0.73). Commercial software results are: RAPID = (2.25 mL, 21.48 mL, 0.63, 0.70), Sphere = (7.57 mL, 17.74 mL, 0.64, 0.70), Vitrea = (6.79 mL, 15.28 mL, 0.63, 0.72). Conclusions: Use of CNNs with multiple input perfusion parameters has shown to be accurate in segmenting infarcts and has the ability to improve clinical workflow by eliminating the need for contralateral hemisphere comparisons.

Assessment of computed tomography perfusion software in predicting spatial location and volume of infarct in acute ischemic stroke patients: a comparison of Sphere, Vitrea, and RAPID.

BACKGROUND: CT perfusion (CTP) infarct and penumbra estimations determine the eligibility of patients with acute ischemic stroke (AIS) for endovascular intervention. This study aimed to determine volumetric and spatial agreement of predicted RAPID, Vitrea, and Sphere CTP infarct with follow-up fluid attenuation inversion recovery (FLAIR) MRI infarct. METHODS: 108 consecutive patients with AIS and large vessel occlusion were included in the study between April 2019 and January 2020 . Patients were divided into two groups: endovascular intervention (n=58) and conservative treatment (n=50). Intervention patients were treated with mechanical thrombectomy and achieved successful reperfusion (Thrombolysis in Cerebral Infarction 2b/2 c/3) while patients in the conservative treatment group did not receive mechanical thrombectomy or intravenous thrombolysis. Intervention and conservative treatment patients were included to assess infarct and penumbra estimations, respectively. It was assumed that in all patients treated conservatively, penumbra converted to infarct. CTP infarct and penumbra volumes were segmented from RAPID, Vitrea, and Sphere to assess volumetric and spatial agreement with follow-up FLAIR MRI. RESULTS: Mean infarct differences (95% CIs) between each CTP software and FLAIR MRI for each cohort were: intervention cohort: RAPID=9.0±7.7 mL, Sphere=-0.2±8.7 mL, Vitrea=-7.9±8.9 mL; conservative treatment cohort: RAPID=-31.9±21.6 mL, Sphere=-26.8±17.4 mL, Vitrea=-15.3±13.7 mL. Overlap and Dice coefficients for predicted infarct were (overlap, Dice): intervention cohort: RAPID=(0.57, 0.44), Sphere=(0.68, 0.60), Vitrea=(0.70, 0.60); conservative treatment cohort: RAPID=(0.71, 0.56), Sphere=(0.73, 0.60), Vitrea=(0.72, 0.64). CONCLUSIONS: Sphere proved the most accurate in patients who had intervention infarct assessment as Vitrea and RAPID overestimated and underestimated infarct, respectively. Vitrea proved the most accurate in penumbra assessment for patients treated conservatively although all software overestimated penumbra.

Automatic radiomic feature extraction using deep learning for angiographic parametric imaging of intracranial aneurysms.

BACKGROUND: Angiographic parametric imaging (API) is an imaging method that uses digital subtraction angiography (DSA) to characterize contrast media dynamics throughout the vasculature. This requires manual placement of a region of interest over a lesion (eg, an aneurysm sac) by an operator. OBJECTIVE: The purpose of our work was to determine if a convolutional neural network (CNN) was able to identify and segment the intracranial aneurysm (IA) sac in a DSA and extract API radiomic features with minimal errors compared with human user results. METHODS: Three hundred and fifty angiographic images of IAs were retrospectively collected. The IAs and surrounding vasculature were manually contoured and the masks put to a CNN tasked with semantic segmentation. The CNN segmentations were assessed for accuracy using the Dice similarity coefficient (DSC) and Jaccard index (JI). Area under the receiver operating characteristic curve (AUROC) was computed. API features based on the CNN segmentation were compared with the human user results. RESULTS: The mean JI was 0.823 (95% CI 0.783 to 0.863) for the IA and 0.737 (95% CI 0.682 to 0.792) for the vasculature. The mean DSC was 0.903 (95% CI 0.867 to 0.937) for the IA and 0.849 (95% CI 0.811 to 0.887) for the vasculature. The mean AUROC was 0.791 (95% CI 0.740 to 0.817) for the IA and 0.715 (95% CI 0.678 to 0.733) for the vasculature. All five API features measured inside the predicted masks were within 18% of those measured inside manually contoured masks. CONCLUSIONS: CNN segmentation of IAs and surrounding vasculature from DSA images is non-inferior to manual contours of aneurysms and can be used in parametric imaging procedures.

Feasibility study for use of angiographic parametric imaging and deep neural networks for intracranial aneurysm occlusion prediction.

BACKGROUND: Angiographic parametric imaging (API), based on digital subtraction angiography (DSA), is a quantitative imaging tool that may be used to extract contrast flow parameters related to hemodynamic conditions in abnormal pathologies such as intracranial aneurysms (IAs). OBJECTIVE: To investigate the feasibility of using deep neural networks (DNNs) and API to predict IA occlusion using pre- and post-intervention DSAs. METHODS: We analyzed DSA images of IAs pre- and post-treatment to extract API parameters in the IA dome and the corresponding main artery (un-normalized data). We implemented a two-step correction to account for injection variability (normalized data) and projection foreshortening (relative data). A DNN was trained to predict a binary IA occlusion outcome: occluded/unoccluded. Network performance was assessed with area under the receiver operating characteristic curve (AUROC) and classification accuracy. To evaluate the effect of the proposed corrections, prediction accuracy analysis was performed after each normalization step. RESULTS: The study included 190 IAs. The mean and median duration between treatment and follow-up was 9.8 and 8.0 months, respectively. For the un-normalized, normalized, and relative subgroups, the DNN average prediction accuracies for IA occlusion were 62.5% (95% CI 60.5% to 64.4%), 70.8% (95% CI 68.2% to 73.4%), and 77.9% (95% CI 76.2% to 79.6%). The average AUROCs for the same subgroups were 0.48 (0.44-0.52), 0.67 (0.61-0.73), and 0.77 (0.74-0.80). CONCLUSIONS: The study demonstrated the feasibility of using API and DNNs to predict IA occlusion using only pre- and post-intervention angiographic information.

Assessment of distal access catheter performance during neuroendovascular procedures: measuring force in three-dimensional patient specific phantoms.

BACKGROUND: The amount of force applied on a device is an important measure to evaluate the endovascular and surgical device manipulations. The measure has not been evaluated for neuroenodvascular procedures. PURPOSE: We aimed to study the use of force measure as a novel approach to test distal access catheter (DAC) performance during catheterization of cervical and intracranial vessels using patient specific 3-dimentional (3D) phantoms. METHODS: Using patient specific 3D phantoms of the cervical and intracranial circulation, we recorded measure of force required to deliver three types of DACs beyond the ophthalmic segment of the internal carotid artery. Six different combinations of DAC-microcatheter-guidewire were tested. We intentionally included what we considered suboptimal combinations of DACs, microcatheters, and guidewires during our experiments to test the feasibility of measuring force under different conditions. A six axis force sensor was secured to the DAC with an adjustable torque used to track axially directed push and pull forces required to navigate the DAC to the target site. RESULTS: In a total of 55 experiments, we found a significant difference in the amount of force used between different DACs (mean force for DAC A, 1.887±0.531N; for DAC B, 2.153±1.280 N; and for DAC C, 1.194±0.521 N, P=0.007). There was also a significant difference in force measures among the six different catheter systems (P=0.035). CONCLUSIONS: Significant difference in the amount of force used between different DACs and catheter systems were recorded. Use of force measure in neuroendovascular procedures on 3D printed phantoms is feasible.

Antimicrobial Peptide Combined with BMP2-Modified Mesenchymal Stem Cells Promotes Calvarial Repair in an Osteolytic Model.

Repair and regeneration of inflammation-induced bone loss remains a clinical challenge. LL37, an antimicrobial peptide, plays critical roles in cell migration, cytokine production, apoptosis, and angiogenesis. Migration of stem cells to the affected site and promotion of vascularization are essential for tissue engineering therapy, including bone regeneration. However, it is largely unknown whether LL37 affects mesenchymal stem cell (MSC) behavior and bone morphogenetic protein 2 (BMP2)-mediated bone repair during the bone pathologic remodeling process. By performing in vitro and in vivo studies with MSCs and a lipopolysaccharide (LPS)-induced mouse calvarial osteolytic bone defect model, we found that LL37 significantly promotes cell differentiation, migration, and proliferation in both unmodified MSCs and BMP2 gene-modified MSCs. Additionally, LL37 inhibited LPS-induced osteoclast formation and bacterial activity in vitro. Furthermore, the combination of LL37 and BMP2 markedly promoted MSC-mediated angiogenesis and bone repair and regeneration in LPS-induced osteolytic defects in mouse calvaria. These findings demonstrate for the first time that LL37 can be a potential candidate drug for promoting osteogenesis and for inhibiting bacterial growth and osteoclastogenesis, and that the combination of BMP2 and LL37 is ideal for MSC-mediated bone regeneration, especially for inflammation-induced bone loss.

The combination of nano-calcium sulfate/platelet rich plasma gel scaffold with BMP2 gene-modified mesenchymal stem cells promotes bone regeneration in rat critical-sized calvarial defects.

BACKGROUND: Mesenchymal stem cells (MSCs) can be differentiated into an osteoblastic lineage in the presence of growth factors (GFs). Platelet-rich plasma (PRP), which can be easily isolated from whole blood, contains a large amount of GFs, and, therefore, promotes bone growth and regeneration. The main goal of this work was to develop and investigate the effect of a new sandwich-like bone scaffold which combines a nano-calcium sulfate (nCS) disc along with PRP fibrin gel (nCS/PRP) with BMP2-modified MSCs on bone repair and regeneration in rat critical-sized calvarial defects. METHODS: We evaluated the cytotoxicity, osteogenic differentiation and mineralization effect of PRP extract on BMP2-modified MSCs and constructed a sandwich-like nCS/PRP scaffold (mimicking the nano-calcium matrix of bone and carrying multi GFs in the PRP) containing BMP2-modified MSCs. The capacity of this multifunctional bone regeneration system in promoting bone repair was assessed in vivo in a rat critical-sized (8 mm) calvarial bone defect model. RESULTS: We developed an optimized nCS/PRP sandwich-like scaffold. Scanning electron microscopy (SEM) results showed that nCS/PRP are polyporous with an average pore diameter of 70-80 µm and the cells can survive in the nCS/PRP scaffold. PRP extract dramatically stimulated proliferation and differentiation of BMP2-modified MSCs in vitro. Our in vivo results showed that the combination of BMP2-modified MSCs and nCS/PRP scaffold dramatically increased new bone regeneration compared with the groups without PRP and/or BMP2. CONCLUSIONS: nCS/PRP scaffolds containing BMP2-modified MSCs successfully promotes bone regeneration in critical-sized bone defects. This system could ultimately enable clinicians to better reconstruct the craniofacial bone and avoid donor site morbidity for critical-sized bone defects.

Three-dimensional printing of MRI-visible phantoms and MR image-guided therapy simulation.

PURPOSE: To demonstrate the use of anatomic MRI-visible three-dimensional (3D)-printed phantoms and to assess process accuracy and material MR signal properties. METHODS: A cervical spine model was generated from computed tomography (CT) data and 3D-printed using an MR signal-generating material. Printed phantom accuracy and signal characteristics were assessed using 120 kVp CT and 3 Tesla (T) MR imaging. The MR relaxation rates and diffusion coefficient of the fabricated phantom were measured and 1 H spectra were acquired to provide insight into the nature of the proton signal. Finally, T2 -weighted imaging was performed during cryoablation of the model. RESULTS: The printed model produced a CT signal of 102 ± 8 Hounsfield unit, and an MR signal roughly 1/3rd that of saline in short echo time/short repetition time GRE MRI (456 ± 36 versus 1526 ± 121 arbitrary signal units). Compared with the model designed from the in vivo CT scan, the printed model differed by 0.13 ± 0.11 mm in CT, and 0.62 ± 0.28 mm in MR. The printed material had T2 ∼32 ms, T2*∼7 ms, T1 ∼193 ms, and a very small diffusion coefficient less than olive oil. MRI monitoring of the cryoablation demonstrated iceball formation similar to an in vivo procedure. CONCLUSION: Current 3D printing technology can be used to print anatomically accurate phantoms that can be imaged by both CT and MRI. Such models can be used to simulate MRI-guided interventions such as cryosurgeries. Future development of the proposed technique can potentially lead to printed models that depict different tissues and anatomical structures with different MR signal characteristics. Magn Reson Med 77:613-622, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Hybrid Biomaterial with Conjugated Growth Factors and Mesenchymal Stem Cells for Ectopic Bone Formation.

Bone is a highly vascularized tissue and efficient bone regeneration requires neovascularization, especially for critical-sized bone defects. We developed a novel hybrid biomaterial comprising nanocalcium sulfate (nCS) and fibrin hydrogel to deliver mesenchymal stem cells (MSCs) and angiogenic factors, vascular endothelial growth factor (VEGF) and fibroblast growth factor 9 (FGF9), to promote neovascularization and bone formation. MSC and growth factor(s)-loaded scaffolds were implanted subcutaneously into mice to examine their angiogenic and osteogenic potential. Micro CT, alkaline phosphatase activity assay, and histological analysis were used to evaluate bone formation, while immunohistochemistry was employed to assess neovessel formation. The presence of fibrin preserved the nCS scaffold structure and promoted de novo bone formation. In addition, the presence of bone morphogenic protein 2-expressing MSC in nCS and fibrin hydrogels improved bone regeneration significantly. While FGF9 alone had no significant effect, the combination FGF9 and VEGF conjugated in fibrin enhanced neovascularization and bone formation more than 4-fold compared to nCS with MSC. Overall, our results suggested that the combination of nCS (to support bone formation) with a fibrin-based VEGF/FGF9 release system (support vascular formation) is an innovative and effective strategy that significantly enhanced ectopic bone formation in vivo.

Stent retriever thrombectomy with the Cover accessory device versus proximal protection with a balloon guide catheter: in vitro stroke model comparison.

BACKGROUND: Recently, an in vitro cerebrovascular occlusion model of the intracranial circulation was developed for testing thrombectomy devices. The Cover accessory (Lazarus Effect; Campbell, California, USA) is a novel nitinol braided mesh device that surrounds the stent retrieval device and thrombus during the retrieval process to help prevent clot fragmentation and embolization. METHODS: Using the in vitro model, after introducing fresh clot into the middle cerebral artery, we compared rates of target vessel recanalization and embolization in new territories (areas in which clot had not been introduced) achieved with the Solitaire Flow Restoration (FR) stent retriever (Covidien, Irvine, California) in conjunction with the use of a conventional guide catheter (control group), a balloon guide catheter (BGC group), and the Cover device (Cover group). RESULTS: In a total of 51 thrombectomy experiments (20 in the control group, 20 in the BGC group, and 11 in the Cover group), successful recanalization (Thrombolysis in Cerebral Infarction 2b-3) was achieved more frequently in the Cover group than in the control group or in the BGC group (p=0.047 and p=0.020, respectively). Embolization of new (previously unaffected) territories occurred in five (25%) experiments from the control group and in three (15%) experiments from the BGC group, whereas no embolization of new territories was seen with Cover device assisted thrombectomy. CONCLUSIONS: Application of the Cover device in this experimental model resulted in higher successful recanalization rates, no embolic events, and was more effective than use of the conventional guide catheter or BGC.

Primary stentriever versus combined stentriever plus aspiration thrombectomy approaches: in vitro stroke model comparison.

BACKGROUND: Artificial stroke models can be used for testing various thrombectomy devices. OBJECTIVE: To determine the value of combined stentriever-aspiration thrombectomy compared with the stentriever-alone approach. METHODS: We designed an in vitro model of the intracranial circulation with a focus on the middle cerebral artery (MCA) that closely resembles the human intracranial circulation. After introducing fresh clot in the MCA, we used conventional biplane angiography and microangiographic fluoroscopy to compare recanalization rates and occurrence of emboli in new, unaffected territory for thrombectomy approaches in which a stentriever (Solitaire flow restoration stentriever, Covidien) was used alone or in combination with continuous manual aspiration through a Navien catheter (Covidien). RESULTS: In a total of 22 experiments (11 for each approach), successful clot delivery to the MCA was achieved in all cases. Successful angiographic recanalization (thrombolysis in cerebral infarction score of 2b-3) was achieved more frequently with the combined stentriever-aspiration approach than with the stentriever-alone approach (in 10 vs 4 experiments, p=0.023). Emboli in new territory occurred in three experiments with the stentriever-alone approach, and none were seen with the combined approach (p=0.21). CONCLUSIONS: The combined stentriever-aspiration approach to thrombectomy leads to better angiographic recanalization rates than use of the stentriever alone. Further experiments are needed to test the value of balloon-guide catheters and aspiration performed using other types of catheters and modes of aspiration.

Endovascular coil embolization of a very small ruptured aneurysm using a novel microangiographic technique: technical note.

Endovascular treatment of very small aneurysms is technically difficult, although recent advances with coils, microcatheters and adjunctive techniques such as balloon- or stent-assisted coiling have improved the outcomes. The microangiographic fluoroscope (MAF) is a new high-resolution x-ray detector developed for neurointerventional procedures in which superior resolution is required within a small field of view. We report the successful coil embolization of a very small ruptured anterior communicating artery aneurysm using the MAF technique. The use of the MAF facilitated the precision of the coiling procedure and was helpful in preventing catheter- and coil-related intraprocedural complications.

The asymmetric vascular stent: efficacy in a rabbit aneurysm model.

BACKGROUND AND PURPOSE: Development of hemodynamic modifying devices to treat intracranial aneurysms is an active area of research. The asymmetrical vascular stent (AVS), a stent containing a low-porosity patch, is such device. We evaluate AVS efficacy in an in vivo intracranial aneurysm model. METHODS: We created 24 elastase rabbit model aneurysms: 13 treated with the AVS, 5 treated with standard coronary stents, and 6 untreated controls. Four weeks after treatment, aneurysms underwent follow-up angiography, cone-beam micro-CT, histological evaluation, and selective electron microscopy scanning. RESULTS: Four rabbits died early in the study: 3 during AVS treatment and 1 control (secondary to intraprocedural vessel injury and an unrelated tumor, respectively). AVS-treated aneurysms exhibited very weak or no aneurysm flow immediately after treatment and no flow in all aneurysms at follow-up. Standard stent-treated aneurysms showed flow both after treatment (5/5) and at follow-up (3/5). All control aneurysms remained patent during the study. Micro-CT scans showed: 9 of 9 scanned AVS aneurysms were occluded, 6 of 9 AVS were ideally placed, and 3 of 9 low-porosity region partially covered the aneurysm neck; standard stent-treated aneurysms were 1 of 5 occluded, 2 of 5 patent, and 2 of 5 partially patent. Histology results demonstrated: for AVS-treated aneurysms, advanced thrombus organization in the (9/9); for standard stent-treated aneurysms, (1/4) no thrombus, (2/4) partially thrombosed, and (1/4) fully thrombosed; for control aneurysms (4/4), no thrombus. CONCLUSIONS: The use of AVS shows promise as a viable new therapeutic in intracranial aneurysm treatment. These data encourage further investigation and provide substantial support to the AVS concept.

Cone-beam micro-CT system based on LabVIEW software.

Construction of a cone-beam computed tomography (CBCT) system for laboratory research usually requires integration of different software and hardware components. As a result, building and operating such a complex system require the expertise of researchers with significantly different backgrounds. Additionally, writing flexible code to control the hardware components of a CBCT system combined with designing a friendly graphical user interface (GUI) can be cumbersome and time consuming. An intuitive and flexible program structure, as well as the program GUI for CBCT acquisition, is presented in this note. The program was developed in National Instrument's Laboratory Virtual Instrumentation Engineering Workbench (LabVIEW) graphical language and is designed to control a custom-built CBCT system but has been also used in a standard angiographic suite. The hardware components are commercially available to researchers and are in general provided with software drivers which are LabVIEW compatible. The program structure was designed as a sequential chain. Each step in the chain takes care of one or two hardware commands at a time; the execution of the sequence can be modified according to the CBCT system design. We have scanned and reconstructed over 200 specimens using this interface and present three examples which cover different areas of interest encountered in laboratory research. The resulting 3D data are rendered using a commercial workstation. The program described in this paper is available for use or improvement by other researchers.