scholarly journals Improved co-registration of ex-vivo and in-vivo cardiovascular magnetic resonance images using heart-specific flexible 3D printed acrylic scaffold combined with non-rigid registration

Author(s):  
John Whitaker ◽  
Radhouene Neji ◽  
Nicholas Byrne ◽  
Esther Puyol-Antón ◽  
Rahul K. Mukherjee ◽  
...  

Abstract Background Ex-vivo cardiovascular magnetic resonance (CMR) imaging has played an important role in the validation of in-vivo CMR characterization of pathological processes. However, comparison between in-vivo and ex-vivo imaging remains challenging due to shape changes occurring between the two states, which may be non-uniform across the diseased heart. A novel two-step process to facilitate registration between ex-vivo and in-vivo CMR was developed and evaluated in a porcine model of chronic myocardial infarction (MI). Methods Seven weeks after ischemia-reperfusion MI, 12 swine underwent in-vivo CMR imaging with late gadolinium enhancement followed by ex-vivo CMR 1 week later. Five animals comprised the control group, in which ex-vivo imaging was undertaken without any support in the LV cavity, 7 animals comprised the experimental group, in which a two-step registration optimization process was undertaken. The first step involved a heart specific flexible 3D printed scaffold generated from in-vivo CMR, which was used to maintain left ventricular (LV) shape during ex-vivo imaging. In the second step, a non-rigid co-registration algorithm was applied to align in-vivo and ex-vivo data. Tissue dimension changes between in-vivo and ex-vivo imaging were compared between the experimental and control group. In the experimental group, tissue compartment volumes and thickness were compared between in-vivo and ex-vivo data before and after non-rigid registration. The effectiveness of the alignment was assessed quantitatively using the DICE similarity coefficient. Results LV cavity volume changed more in the control group (ratio of cavity volume between ex-vivo and in-vivo imaging in control and experimental group 0.14 vs 0.56, p < 0.0001) and there was a significantly greater change in the short axis dimensions in the control group (ratio of short axis dimensions in control and experimental group 0.38 vs 0.79, p < 0.001). In the experimental group, prior to non-rigid co-registration the LV cavity contracted isotropically in the ex-vivo condition by less than 20% in each dimension. There was a significant proportional change in tissue thickness in the healthy myocardium (change = 29 ± 21%), but not in dense scar (change = − 2 ± 2%, p = 0.034). Following the non-rigid co-registration step of the process, the DICE similarity coefficients for the myocardium, LV cavity and scar were 0.93 (±0.02), 0.89 (±0.01) and 0.77 (±0.07) respectively and the myocardial tissue and LV cavity volumes had a ratio of 1.03 and 1.00 respectively. Conclusions The pattern of the morphological changes seen between the in-vivo and the ex-vivo LV differs between scar and healthy myocardium. A 3D printed flexible scaffold based on the in-vivo shape of the LV cavity is an effective strategy to minimize morphological changes in the ex-vivo LV. The subsequent non-rigid registration step further improved the co-registration and local comparison between in-vivo and ex-vivo data.

2015 ◽  
Vol 118 (6) ◽  
pp. 692-698 ◽  
Author(s):  
Audrey Lee-Gosselin ◽  
David Gendron ◽  
Marie-Renée Blanchet ◽  
David Marsolais ◽  
Ynuk Bossé

Airway hyperresponsiveness to a spasmogenic challenge such as methacholine, and an increased baseline tone measured by the reversibility of airway obstruction with a bronchodilator, are two common features of asthma. However, whether the increased tone influences the degree of airway responsiveness to a spasmogen is unclear. Herein, we hypothesized that increased tone augments airway responsiveness in vivo by increasing the contractile capacity of airway smooth muscle (ASM). Anesthetized, tracheotomized, paralyzed, and mechanically ventilated mice were either exposed (experimental group) or not (control group) to tone for 20 min, which was elicited by nebulizing serial small doses of methacholine. Respiratory system resistance was monitored during this period and the peak response to a large cumulative dose of methacholine was then measured at the end of 20 min to assess and compare the level of airway responsiveness between groups. To confirm direct ASM involvement, the contractile capacity of excised murine tracheas was measured with and without preexposure to tone elicited by either methacholine or a thromboxane A2 mimetic (U46619). Distinct spasmogens were tested because the spasmogens liable for increased tone in asthma are likely to differ. The results indicate that preexposure to tone increases airway responsiveness in vivo by 126 ± 37% and increases the contractile capacity of excised tracheas ex vivo by 23 ± 4% for methacholine and 160 ± 63% for U46619. We conclude that an increased tone, regardless of whether it is elicited by a muscarinic agonist or a thromboxane A2 mimetic, may contribute to airway hyperresponsiveness by increasing the contractile capacity of ASM.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 44-44 ◽  
Author(s):  
Daniel N. Costa ◽  
Yonatan Chatzinoff ◽  
Niccolo M. Passoni ◽  
Payal Kapur ◽  
Claus G Roehrborn ◽  
...  

44 Background: A critical requirement for imaging-pathology correlation is adequate image registration. Since the prostate is deformable, sectioning the gland in a plane similar to imaging is challenging. To improve the in vivo imaging and ex vivo histology image registration, 3D-printed, patient-specific, MRI-derived molds (PSMs) for whole-mount processing have been proposed. This study compared the anatomical registration of preoperative MRI and prostate whole-mounts obtained with PSMs versus conventional whole-mount sectioning (WMS). Methods: Based on an a priori power analysis, 50 men who underwent 3T prostate MRI followed by radical prostatectomy were included. Two blinded and independent readers (R1, R2) outlined the contours of the gland and of the tumor in the MRI using regions of interest (ROIs). These were compared with the ROIs from the whole-mount histology, the reference standard, using PSMs in the study group (n=25) or conventional WMS in the control group (n=25). The spatial overlap across the MRI and histology data sets was calculated using the Dice similarity coefficient (DSC) for the prostate overall and tumor. Results were compared using Wilcoxon rank sum test. Results: The MRI-histopathology anatomical registration for the prostate gland overall and the tumor were significantly superior with the use of PSMs than with the use of WMS for both readers (Table). Conclusions: The use of PSMs for prostate specimen whole-mount sectioning provides significantly superior anatomical registration of in vivo multiparametric MRI and ex vivo prostate whole-mounts than conventional WMS. The use of PSMs should facilitate the exchange of information across imaging and pathology required for research and patient care. [Table: see text]


2021 ◽  
Vol 10 (20) ◽  
pp. 4718
Author(s):  
Diana Florina Nica ◽  
Alin Gabriel Gabor ◽  
Virgil-Florin Duma ◽  
Vlad George Tudericiu ◽  
Anca Tudor ◽  
...  

Background and Objectives: The aim of this study is to demonstrate the increased efficiency achieved by dental practitioners when carrying out an ex vivo training process on 3D-printed maxillaries before performing in vivo surgery. Materials and Methods: This developed ex vivo procedure comprises the following phases: (i) scanning the area of interest for surgery; (ii) obtaining a 3D virtual model of this area using Cone Beam Computed Tomography (CBCT); (iii) obtaining a 3D-printed model (based on the virtual one), on which (iv) the dental practitioner simulates/rehearses ex vivo (most of) the surgery protocol; (v) assess with a new CBCT the 3D model after simulation. The technical steps of sinus augmentation and implant insertion could be performed on the corresponding 3D-printed hemi-maxillaries prior to the real in vivo surgery. Two study groups were considered, with forty patients divided as follows: Group 1 comprises twenty patients on which the developed simulation and rehearsal procedure was applied; Group 2 is a control one which comprises twenty patients on which similar surgery was performed without this procedure (considered in order to compare operative times without and with rehearsals). Results: Following the ex vivo training/rehearsal, an optimal surgery protocol was developed for each considered case. The results of the surgery on patients were compared with the results obtained after rehearsals on 3D-printed models. The performed quantitative assessment proved that, using the proposed training procedure, the results of the in vivo surgery are not significantly different (p = 0.089) with regard to the ex vivo simulation for both the mezio-distal position of the implant and the distance from the ridge margin to sinus window. On the contrary, the operative time of Group 1 was reduced significantly (p = 0.001), with an average of 20% with regard to in vivo procedures performed without rehearsals (on the control Group 2). Conclusions: The study demonstrated that the use of 3D-printed models can be beneficial to dental surgeon practitioners, as well as to students who must be trained before performing clinical treatments.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 382-382
Author(s):  
Xin Guan ◽  
Meng Qin ◽  
Yu Zhang ◽  
Zhihua Ren ◽  
Wenhong Jiang ◽  
...  

Abstract The ex vivo induction of megakaryocytes/platelets of hematopoietic stem cells represent an effective treatment for thrombocytopenia. We have previously reported a clinically feasible "two-stage culture system" for expanding CD34+ cells and producing megakaryocytes/platelets. With this culture system one cord-blood unit (2 × 106 - 5 × 106 CD34+ cells) yields sufficient megakaryocytes/platelets for treating up to 85 patients (with an average weight of 70 kg and infusion cell number 5.45 × 106 cells/kg). The induced human megakaryocytic cells were capable of producing functional platelets in xenotransplantation mouse model. Here, we further tested the safety and feasibility of ex vivo generated megakaryocytic progenitors/platelets in a myeloablative non-human primate model. Mobilized peripheral blood CD34+ cells of cynomolgus monkeys (Macaca fascicularis) wereisolated after daily administration of G-CSF (100 μg/kg/day) and SCF (50 μg/kg/day) for five days. Expansion and subsequent differentiation of CD34+ cells and megakaryocytic progenitor cells were performed in a modified IMDM basal medium supplemented with various cytokine combinations including stem cell factor, Flt-3 ligand, thrombopoietin, interleukin 3, StemRegenin 1, interleukin 6 for 8 days. The expansion and differentiation processes were closely monitored by flow cytometry for expression of cell surface markers. In vitro morphological identification and CFU assays were carried out for monkey megakaryocytic progenitors. Furthermore, safety and efficacy of induced megakaryocytic progenitor cells were evaluated in vivo by using a thrombocytopenia model of monkeys. Briefly, cynomolgus monkeys were administered with carboplatin at a dose of 8 mg/kg/day on days 1, 2 and 3. On day 7 after the first carboplatin injection, the experimental group monkeys were infused with megakaryocytic progenitor cells (4.6±1.2 × 106/kg ) labeled with anti-monkey IgG-microbead-FITC conjugates. Negative control group was treated with normal saline. Peripheral blood and bone marrow from the tested animals were obtained for analyzing cell differentiation at various times. In vivo bleeding time was recorded to assess the matured platelet function, which was the time length of the bleeding to stop by making a cut in the forearm of the monkeys. After culturing for 8 days, total cells were expanded up to 13.65±3.79-fold. Analysis of the percentage of component cells further showed that CD34+, CD41+, and CD34+/CD41+ megakaryocytic progenitor cells were 46.8%±3.2%, 22.9%±4.6%, and 20.3%±2.8%, respectively. Induced megakaryocytic cells were morphologically distinguishable as they were much larger than CD34+ cells with apparent lobular nuclei. CFU analysis revealed that they increased 12±4.3-fold on day 8 as compared with day 1. In the experimental group, platelet count nadir occurred on day 14 or 15 with 40% of normal value and completely recovered to the normal value on day 26. On the other hand, the nadir of the platelet count in the control group occurred on day 19 or 20 with 20% of normal value and recovered to the normal on day 32. During the nadir phase (from days 14 to 20), the in vivo bleeding time of experimental group was considered normal (6-7.5 minutes) relative to untreated normal monkey values (range 5-7 minutes), whereas it was longer (~8.5 minutes) in control group. Likewise, the nadir of white blood cell (WBC) count (with 45% of the normal value) occurred on day 17, which completely recovered on day 22 for the monkeys infused with induced megakaryocytic progenitors/ platelets. On the other hand, the nadir of WBC count of the control group was 35% of normal value on day 19, which recovered to the normal on day 36. Fifteen days after infusion, flow cytometry and fluorescent microscope analyses showed that about 1% of fluorescent cells remained in bone marrow, indicating successful engraftment of CD34+ stem/progenitor cells in the infused cell preparation. The infused monkeys have survived with no apparent abnormalities for more than one year. Combined, our results strongly suggest that functional human megakaryocytes/platelets can be produced in a large-scale from CD34+ cells for potential clinical application. More importantly, induced non-human primate megakaryocytic progenitors/platelets can be safely administrated to myelosuppressive monkeys, contributing to platelet recovery and early engraftment. Disclosures Qin: Biopharmagen. corp: Employment. Ren:Biopharmagen corp: Employment. Jiang:Biopharmagen.corp: Employment.


2017 ◽  
Vol 26 (2) ◽  
pp. 243-251 ◽  
Author(s):  
Michael B. Jirjis ◽  
Chris Valdez ◽  
Aditya Vedantam ◽  
Brian D. Schmit ◽  
Shekar N. Kurpad

OBJECTIVE The aims of this study were to determine if the morphological and functional changes induced by neural stem cell (NSC) grafts after transplantation into the rodent spinal cord can be detected using MR diffusion tensor imaging (DTI) and, furthermore, if the DTI-derived mean diffusivity (MD) metric could be a biomarker for cell transplantation in spinal cord injury (SCI). METHODS A spinal contusion was produced at the T-8 vertebral level in 40 Sprague Dawley rats that were separated into 4 groups, including a sham group (injury without NSC injection), NSC control group (injury with saline injection), co-injection control group (injury with Prograf), and the experimental group (injury with NSC and Prograf injection). The NSC injection was completed 1 week after injury into the site of injury and the rats in the experimental group were compared to the rats from the sham, NSC control, and co-injection groups. The DTI index, MD, was assessed in vivo at 2, 5, and 10 weeks and ex vivo at 10 weeks postinjury on a 9.4-T Bruker scanner using a spin-echo imaging sequence. DTI data of the cervical spinal cord from the sham surgery, injury with saline injection, injury with injection of Prograf only, and injury with C17.2 NSC and Prograf injection were examined to evaluate if cellular proliferation induced by intrathoracic C17.2 engraftment was detectable in a noninvasive manner. RESULTS At 5 weeks after injury, the average fractional anisotropy, longitudinal diffusion (LD) and radial diffusion (RD) coefficients, and MD of water (average of the RD and LD eigenvalues in the stem cell line–treated group) increased to an average of 1.44 × 10−3 sec/mm2 in the cervical segments, while the control groups averaged 0.98 × 10−3 s/mm2. Post hoc Tukey's honest significant difference tests demonstrated that the transplanted stem cells had significantly higher MD values than the other groups (p = 0.032 at 5 weeks). In vivo and ex vivo findings at 10 weeks displayed similar results. This statistical difference between the stem cell line and the other groups was maintained at the 10-week postinjury in vivo and ex vivo time points. CONCLUSIONS These results indicate that the DTI-derived MD metric collected from noninvasive imaging techniques may provide useful biomarker indices for transplantation interventions that produce changes in the spinal cord structure and function. Though promising, the results demonstrated here suggest additional work is needed before implementation in a clinical setting.


Author(s):  
Hana M. Hammad ◽  
Amer Imraish ◽  
Maysa Al-Hussaini ◽  
Malek Zihlif ◽  
Amani A. Harb ◽  
...  

Objective: Achillea fragrantissima L. (Asteraceae) is a traditionally used medicinal herb in the rural communities of Jordan. Methods: The present study evaluated the efficacy of the ethanol extract of this species on angiogenesis in both, ex vivo using rat aortic ring assay and in vivo using rat excision wound model. Results: In concentrations of 50 and 100 µg/ml, the ethanol extract showed angiogenic stimulatory effect and significantly increased length of capillary protrusions around aorta rings of about 60% in comparison to those of untreated aorta rings. In MCF-7 cells, the ethanol extract of A. fragrantissima stimulates the production of VEGF in a dose-dependent manner. 1% and 5% of ethanol extract of A. fragrantissima containing vaseline based ointment was applied on rat excision wounds for six days and was found to be effective in wound healing and maturation of the scar. Both preparations resulted in better wound healing when compared to the untreated control group and vaseline-treated group. This effect was comparable to that induced by MEBO, the positive control. Conclusion: The results indicate that A. fragrantissima has a pro-angiogenic effect, which may act through the VEGF signaling pathway.


2021 ◽  
pp. 155335062110624
Author(s):  
Jing Yang ◽  
Penghui Ni ◽  
Lina Zhang ◽  
Zhanxin Lu ◽  
Dapeng Liu ◽  
...  

Background This study aimed to evaluate a personalized 3D-printed percutaneous vertebroplasty positioning module and navigation template based on preoperative CT scan data that was designed to treat patients with vertebral compression fractures caused by osteoporosis. Methods A total of 22 patients with vertebral compression fractures admitted to our hospital were included in the study. Positioning was performed with the new 3D-printed positioning module, and the navigation template was used for patients in the experimental group, and the traditional perspective method was used for patients in the control group. The experimental group consisted of 11 patients, 2 males and 9 females, with a mean age of 67.27 ± 11.86 years (range: 48 to 80 years), and the control group consisted of 11 patients, 3 males and 8 females, with a mean age of 74.27 ± 7.24 years (range: 63 to 89 years). The puncture positioning duration, number of intraoperative fluoroscopy sessions, and preoperative and postoperative visual analog scale (VAS) scores were statistically analyzed in both groups. Results The experimental group had shorter puncture positioning durations and fewer intraoperative fluoroscopy sessions than the control group, and the differences were statistically significant (P < .05). There were no significant differences in age or preoperative or postoperative VAS scores between the two groups (P > .05). Conclusions The new 3D-printed vertebroplasty positioning module and navigation template shortened the operation time and reduced the number of intraoperative fluoroscopy sessions. It also reduced the difficulty in performing percutaneous vertebroplasty and influenced the learning curve of senior doctors learning this operation to a certain degree.


2021 ◽  
pp. 34-43
Author(s):  
Evgeniia A. Grigoreva ◽  
Valentina S. Gordova ◽  
Valentina E. Sergeeva ◽  
Alina T. Smorodchenko

The article presents data on the long-term effect (nine months) of a silicon compound supplied with drinking water – nonahydrate sodium metasilicate (10 mg/l in terms of silicon), on CD68-positive macrophages in the liver and spleen of laboratory rats. Changes in the morphological characteristics of this cell population were found. There was a decrease in the average cell area (in the liver of the control group of rats, the average macrophage area was 179.23±5.94 microns2, and in the group receiving silicon with drinking water – 117.04±3.35 microns2; in the spleen-136.02±3.93 microns2 and 103.44±2.8 microns2, respectively). Macrophages in the liver preparations of the experimental group of rats had a fewer processes and a darker cytoplasmic membrane. The number of macrophages in the liver per unit area was comparable, for the control group of rats it was 18.78±1.24, and for the rats that received with water with the addition of silicon – 19.41±0.75 cells. CD68+ macrophages of the red splenic pulp in laboratory rats that received silicon also underwent the following morphological changes: they were located in a denser way and had fewer processes, while the number of macrophages per unit area was 73.7±2.3 for the control group, 91.6±5.0-for the experimental group, respectively. The distance between them did not change. There was a change in the intensity of CD68 expression on the surface of the cytoplasmic membrane and in the cytoplasm of liver and spleen macrophages. These changes can be interpreted as the adaptive ability of liver and spleen macrophages to silicon introduced with drinking water. Given the heterogeneity of the macrophage population in the liver and spleen, further studies using markers for different subpopulations of macrophages are needed to clarify their role in the response of tissues to silicon supplied with drinking water.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Matthew H Park ◽  
Annabel Imbrie-moore ◽  
Yuanjia Zhu ◽  
Hanjay Wang ◽  
Michael J Paulsen ◽  
...  

Introduction: Advances in ex vivo heart simulation have enabled the study of valvular biomechanics, disease pathologies, and repair strategies. However, these simulators test the valves in isolation, which does not fully replicate in vivo physiology. We hypothesize that by engineering a simulator that preserves the aortomitral junction, we can better recreate pathophysiologies such as systolic anterior motion (SAM). Here, we present a new heart simulator that preserves and manipulates the native aortomitral physiology. Methods: Our simulator is comprised of three subsystems: the ventricular chamber, atrial chamber, and aortic chamber (Fig A, B). The heart is excised at the apex to preserve the papillary muscles, and the left ventricle, atrial cuff, and aorta are fixed to their respective chambers via hemostatic suturing to 3D-printed elastomeric rings. The chambers are equipped with pressure and flow sensors, and a linear piston pump generates physiologic pressures and flows. The atrial and aortic chambers are mounted on 5-degree-of-freedom arms. To demonstrate system function, we manipulated the aortomitral angle and measured aortic cardiac output. Results: In our testing, we evaluated two unique configurations of an explanted porcine heart, of which the aortomitral angles spanned the SAM predictive risk threshold of <120° (Fig C, D). From the flow readings, we measured a 36% reduction in aortic cardiac output upon decreasing the aortomitral angle by 25°. Conclusions: This work highlights the design and development of an ex vivo heart simulator capable of modeling native aortomitral physiology. Our results point to a clear direction for future experimentation, particularly evaluating the biomechanical changes of the heart based on the aortomitral angle. Future work will utilize this platform to create new models and repair techniques to ultimately improve clinical care of valvular pathologies.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Hui Hua ◽  
Jiawei Cheng ◽  
Wenbo Bu ◽  
Juan Liu ◽  
Weiwei Ma ◽  
...  

Aim. To determine whether 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is effective in combating ultraviolet A- (UVA-) induced oxidative photodamage of hairless mice skin in vivo and human epidermal keratinocytes in vitro. Methods. In in vitro experiments, the human keratinocyte cell line (HaCaT cells) was divided into two groups: the experimental group was treated with ALA-PDT and the control group was left untreated. Then, the experimental group and the control group of cells were exposed to 10 J/m2 of UVA radiation. ROS, O2− species, and MMP were determined by fluorescence microscopy; p53, OGG1, and XPC were determined by Western blot analysis; apoptosis was determined by flow cytometry; and 8-oxo-dG was determined by immunofluorescence. Moreover, HaCaT cells were also treated with ALA-PDT. Then, SOD1 and SOD2 were examined by Western blot analysis. In in vivo experiments, the dorsal skin of hairless mice was treated with ALA-PDT or saline-PDT, and then, they were exposed to 20 J/m2 UVA light. The compound 8-oxo-dG was detected by immunofluorescence. Conclusion. In human epidermal keratinocytes and hairless mice skin, UVA-induced oxidative damage can be prevented effectively with ALA-PDT pretreatment.


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