Effectiveness of Personalized Hippocampal Network-Targeted Stimulation in Alzheimer Disease: A Randomized Clinical Trial.

Importance: Repetitive transcranial magnetic stimulation (rTMS) has emerged as a safe and promising intervention for Alzheimer disease (AD). Objective: To investigate the effect of a 4-week personalized hippocampal network-targeted rTMS on cognitive and functional performance, as well as functional connectivity in AD. Design, Setting, and Participants: This randomized clinical trial, which was sham-controlled and masked to participants and evaluators, was conducted between May 2020 and April 2022 at a single Korean memory clinic. Eligible participants were between ages 55 and 90 years and had confirmed early AD with evidence of an amyloid biomarker. Participants who met the inclusion criteria were randomly assigned to receive hippocampal network-targeted rTMS or sham stimulation. Participants received 4-week rTMS treatment, with assessment conducted at weeks 4 and 8. Data were analyzed between April 2022 and January 2024. Interventions: Each patient received 20 sessions of personalized rTMS targeting the left parietal area, functionally connected to the hippocampus, based on fMRI connectivity analysis over 4 weeks. The sham group underwent the same procedure, excluding actual magnetic stimulation. A personalized 3-dimensional printed frame to fix the TMS coil to the optimal target site was produced. Main Outcomes and Measures: The primary outcome was the change in the AD Assessment Scale-Cognitive Subscale test (ADAS-Cog) after 8 weeks from baseline. Secondary outcomes included changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SOB) and Seoul-Instrumental Activity Daily Living (S-IADL) scales, as well as resting-state fMRI connectivity between the hippocampus and cortical areas. Results: Among 30 participants (18 in the rTMS group; 12 in the sham group) who completed the 8-week trial, the mean (SD) age was 69.8 (9.1) years; 18 (60%) were female. As the primary outcome, the change in ADAS-Cog at the eighth week was significantly different between the rTMS and sham groups (coefficient [SE], -5.2 [1.6]; P = .002). The change in CDR-SOB (-4.5 [1.4]; P = .007) and S-IADL (1.7 [0.7]; P = .004) were significantly different between the groups favoring rTMS groups. The fMRI connectivity analysis revealed that rTMS increased the functional connectivity between the hippocampus and precuneus, with its changes associated with improvements in ADAS-Cog (r = -0.57; P = .005). Conclusions and Relevance: This randomized clinical trial demonstrated the positive effects of rTMS on cognitive and functional performance, and the plastic changes in the hippocampal-cortical network. Our results support the consideration of rTMS as a potential treatment for AD. Trial Registration: ClinicalTrials.gov Identifier: NCT04260724.

The result of prospective evaluation of 3-dimensional printing-aided extensive thoracoabdominal aorta repair.

Objectives: Paraplegia is a distressing complication after open thoracoabdominal aortic aneurysm (TAAA) repair, and revascularization of T8-L2-level segmental arteries is considered pivotal to prevent paraplegia. We employed 3-dimensional (3D) printing to efficiently revascularize segmental/visceral arteries and prospectively evaluated its safety and efficacy. Methods: From January 1, 2020, to June 30, 2022, we prospectively enrolled patients of extent I, II, or III TAAA repair. Guidance models were 3D-printed based on preoperative computed tomography, and multibranched aortic grafts were manually constructed upon this model before surgery. The composite outcome of operative mortality, permanent stroke, and permanent spinal cord deficit (SCD) was compared with the historical control group (n = 77, in 2015-2020), subjected to similar TAAA repair without 3D printing. Results: A total of 38 patients (58.6 ± 13.2 years) underwent open TAAA repair with the aid of 3D printing. Extent I, II, and III repairs were performed in 14 (36.8%), 17 (44.7%), and 7 (18.4%), respectively. Concomitant arch repair and bi-iliac reconstruction were performed in 7 (18.4%) and 6 patients (15.8%), respectively. Mean pump time was 107.7 ± 55.5 minutes. Operative mortality, permanent stroke, and permanent SCD each occurred in 1 patient (2.6%), and the incidence of the composite outcome was 7.9% (3/38). In the control group, mean pump time was 166.0 ± 83.9 minutes, significantly longer than the 3D-printing group (P < .001), and operative mortality, permanent stroke, permanent SCD, and the composite outcome occurred in 7 (9.1%), 9 (11.7%), 8 (10.4%), and 19 (24.7%), respectively. Conclusions: Open repairs of extensive TAAA with 3D printing showed favorable safety and efficacy, which need further validation by larger studies.

IntraBrain Injector (IBI): A Stereotactic-Guided Device for Repeated Delivery of Therapeutic Agents Into the Brain Parenchyma.

BACKGROUND: To deliver therapeutics into the brain, it is imperative to overcome the issue of the blood-brain-barrier (BBB). One of the ways to circumvent the BBB is to administer therapeutics directly into the brain parenchyma. To enhance the treatment efficacy for chronic neurodegenerative disorders, repeated administration to the target location is required. However, this increases the number of operations that must be performed. In this study, we developed the IntraBrain Injector (IBI), a new implantable device to repeatedly deliver therapeutics into the brain parenchyma. METHODS: We designed and fabricated IBI with medical grade materials, and evaluated the efficacy and safety of IBI in 9 beagles. The trajectory of IBI to the hippocampus was simulated prior to surgery and the device was implanted using 3D-printed adaptor and surgical guides. Ferumoxytol-labeled mesenchymal stem cells (MSCs) were injected into the hippocampus via IBI, and magnetic resonance images were taken before and after the administration to analyze the accuracy of repeated injection. RESULTS: We compared the planned vs. insertion trajectory of IBI to the hippocampus. With a similarity of 0.990 ± 0.001 (mean ± standard deviation), precise targeting of IBI was confirmed by comparing planned vs. insertion trajectories of IBI. Multiple administrations of ferumoxytol-labeled MSCs into the hippocampus using IBI were both feasible and successful (success rate of 76.7%). Safety of initial IBI implantation, repeated administration of therapeutics, and long-term implantation have all been evaluated in this study. CONCLUSION: Precise and repeated delivery of therapeutics into the brain parenchyma can be done without performing additional surgeries via IBI implantation.

Utilizing patient-specific 3D printed guides for graft reconstruction in thoracoabdominal aortic repair.

In thoracoabdominal aortic aneurysm repair, repairing the visceral and segmental arteries is challenging. Although there is a pre-hand-sewn and multi-branched graft based on the conventional image-based technique, it has shortcomings in precisely positioning and directing the visceral and segmental arteries. Here, we introduce two new reconstruction techniques using patient-specific 3D-printed graft reconstruction guides: (1) model-based technique that presents the projected aortic graft, visualizing the main aortic body and its major branches and (2) guide-based technique in which the branching vessels in the visualization model are replaced by marking points identifiable by tactile sense. We demonstrate the effectiveness by evaluating conventional and new techniques based on accuracy, marking time requirement, reproducibility, and results of survey to surgeons on the perceived efficiency and efficacy. The graft reconstruction guides cover the segmentation, design, fabrication, post-processing, and clinical application of open surgical repair of thoracoabdominal aneurysm, and proved to be efficient for accurately reconstructing customized grafts.

Case Report: A 3D-Printed Surgical Guide for Breast-Conserving Surgery After Neoadjuvant Chemotherapy.

BACKGROUND: A challenging problem for patients undergoing breast-conserving surgery after neoadjuvant chemotherapy (NACT) is the accuracy of preoperative tumor localization. After chemotherapy, the original tumor is likely to shrink or scatter dramatically or even show complete remission. For breast-conserving surgery, the development of a guidance device to accurately estimate the resection area is imperative. CASE PRESENTATION: We produced a three-dimensional (3D)-printed breast surgical guide (BSG) based on prone and supine magnetic resonance imaging (MRI). This device was tested on a patient who underwent breast-conserving surgery after NACT. Both ultrasonography and MRI revealed that the tumor shrank substantially after NACT. Identifying the target tumor area using pre-NACT MRI was feasible, and the tumor was safely removed with clear resection margins. CONCLUSION: The BSG has several advantages over conventional methods for tumor localization after NACT. In particular, the BSG provided precise quantitative MRI information about the tumor area.

Differences between 3D isovoxel fat suppression VIBE MRI and CT models of proximal femur osseous anatomy: A preliminary study for bone tumor resection planning.

PURPOSE: To evaluate the osseous anatomy of the proximal femur extracted from a 3D-MRI volumetric interpolated breath-hold (VIBE) sequence using either a Dixon or water excitation (WE) fat suppression method, and to measure the overall difference using CT as a reference standard. MATERIAL AND METHODS: This retrospective study reviewed imaging of adult patients with hip pain who underwent 3D hip MRI and CT. A semi-automatically segmented CT model served as the reference standard, and MRI segmentation was performed manually for each unilateral hip joint. The differences between Dixon-VIBE-3D-MRI vs. CT, and WE-VIBE-3D-MRI vs. CT, were measured. Equivalence tests between Dixon-VIBE and WE-VIBE models were performed with a threshold of 0.1 mm. Bland-Altman plots and Lin's concordance-correlation coefficient were used to analyze the agreement between WE and Dixon sequences. Subgroup analyses were performed for the femoral head/neck, intertrochanteric, and femoral shaft areas. RESULTS: The mean and maximum differences between Dixon-VIBE-3D-MRI vs. CT were 0.2917 and 3.4908 mm, respectively, whereas for WE-VIBE-3D-MRI vs. CT they were 0.3162 and 3.1599 mm. The mean differences of the WE and Dixon methods were equivalent (P = 0.0292). However, the maximum difference was not equivalent between the two methods and it was higher in WE method. Lin's concordance-correlation coefficient showed poor agreement between Dixon and WE methods. The mean differences between the CT and 3D-MRI models were significantly higher in the femoral shaft area (P = 0.0004 for WE and P = 0.0015 for Dixon) than in the other areas. The maximum difference was greatest in the intertrochanteric area for both techniques. CONCLUSION: The difference between 3D-MR and CT models were acceptable with a maximal difference below 3.5mm. WE and Dixon fat suppression methods were equivalent. The mean difference was highest at the femoral shaft area, which was off-center from the magnetization field.

Breast-Conserving Surgery after Neoadjuvant Chemotherapy Using a Three-Dimensional-Printed Surgical Guide Based on Supine Magnetic Resonance Imaging: A Case Report.

Tumor localization in patients receiving neoadjuvant chemotherapy (NACT) is challenging because substantial therapeutic remission of the original tumor after NACT is often noted. Currently, there is no guidance device that allows for an accurate estimation of the resection range in breast-conserving surgery after NACT. To increase the accuracy of tumor resection, we used a 3-dimensional-printed breast surgical guide based on magnetic resonance imaging (MRI) in the supine position for a breast cancer patient who underwent breast-conserving surgery after NACT. Using this device, the breast tumor with apparent therapeutic changes after NACT on imaging was successfully removed with clear resection margins by identifying the original tumor site in the affected breast. Irrespective of whether the residual tumor area after NACT is well defined, it is possible to confirm and target the tumor area on pre-NACT MRI using this device.

Production of ERCP training model using a 3D printing technique (with video).

BACKGROUND: ERCP training models are very different in terms of anatomical differences, ethical issues, storage problems, realistic tactile sensation, durability and portability. There is no easy way to select an optimized model for ERCP training. If the ERCP training model could be made as a soft silicone model using 3D printing technique, it would have numerous advantages over the models presented so far. The purpose of this study was to develop an optimized ERCP training model using a 3D printing technique and to try to find ways for implementing various practical techniques. METHODS: All organ parts of this model were fabricated using silicone molding techniques with 3D printing. Especially, various anatomy of the ampulla of Vater and common bile duct (CBD) were creatively designed for different diagnostic and therapeutic procedures. In order to manufacture each of the designed organ parts with silicone, a negative part had to be newly designed to produce the molder. The negative molders were 3D printed and then injection molding was applied to obtain organ parts in silicone material. The eight different types of ampulla and CBD were repeatedly utilized and replaced to the main system as a module-type. RESULTS: ERCP training silicone model using 3D technique was semi-permanently used to repeat various ERCP procedures. All ERCP procedures using this model could be observed by real-time fluoroscopic examination as well as endoscopic examination simultaneously. Using different ampulla and CBD modules, basic biliary cannulation, difficult cannulation, stone extraction, mechanical lithotripsy, metal stent insertion, plastic stent insertion, and balloon dilation were successfully and repeatedly achieved. Endoscopic sphincterotomy was also performed on a specialized ampulla using a Vienna sausage. After repeat procedures and trainings, all parts of organs including the ampulla and CBD modules were not markedly damaged or deformed. CONCLUSIONS: We made a specialized ERCP training silicon model with 3D printing technique. This model is durable, relatively cheap and easy to make, and thus allows the users to perform various specialized ERCP techniques, which increases its chances of being a good ERCP training model.

Breast tumor movements analysis using MRI scans in prone and supine positions.

We quantitatively evaluated breast tumor movement and volume changes between magnetic resonance imaging (MRI) scans in prone and supine positions. Twenty-seven breast tumor patients who received neoadjuvant systemic therapy (NST) for breast-conserving surgery were studied. Before and after NST, MRI scans in prone and supine positions were performed immediately. Tumor segmentation, volume, and position of tumors were evaluated in both positions. Average tumor volumes in prone and supine positions did not significantly differ (p = 0.877). Tumor movement from prone to supine positions from the origin of the bottom center of the sternum was strongly correlated with the distance from the tumor center to the chest wall (r = 0.669; p < 0.05). Tumor changes from prone to supine positions measured from the origin of the nipple depended on the location of the tumor in the breast. The prone-to-supine movement of all tumors from the origin of the bottom center of the sternum tended to move outward from the sagittal centerline of the body on the coronal plane, to the inside of the body on the sagittal plane, and outward and downward close to the body on the axial plane, which might help in planning operations using prone MRI in supine-position breast cancer surgery.

Stereotaxic endoscopy for the ocular imaging of awake, freely moving animal models.

Stereotaxic instruments are increasingly used in research animals for the study of disease, but typically require restraints and anesthetic procedures. A stereotaxic head mount that enables imaging of the anterior chamber of the eye in alert and freely mobile mice is presented in this study. The head mount is fitted based on computed tomography scans and manufactured using 3D printing. The system is placed noninvasively using temporal mount bars and a snout mount, without breaking the skin or risking suffocation, while an instrument channel stabilizes the ocular probes. With a flexible micro-endoscopic probe and a confocal scanning laser microscopy system, <20 µm resolution is achieved in vivo with a field of view of nearly 1 mm. Discomfort is minimal, and further adaptations for minimally invasive neuroscience, optogenetics and auditory studies are possible.

Active learning for accuracy enhancement of semantic segmentation with CNN-corrected label curations: Evaluation on kidney segmentation in abdominal CT.

Segmentation is fundamental to medical image analysis. Recent advances in fully convolutional networks has enabled automatic segmentation; however, high labeling efforts and difficulty in acquiring sufficient and high-quality training data is still a challenge. In this study, a cascaded 3D U-Net with active learning to increase training efficiency with exceedingly limited data and reduce labeling efforts is proposed. Abdominal computed tomography images of 50 kidneys were used for training. In stage I, 20 kidneys with renal cell carcinoma and four substructures were used for training by manually labelling ground truths. In stage II, 20 kidneys from the previous stage and 20 newly added kidneys were used with convolutional neural net (CNN)-corrected labelling for the newly added data. Similarly, in stage III, 50 kidneys were used. The Dice similarity coefficient was increased with the completion of each stage, and shows superior performance when compared with a recent segmentation network based on 3D U-Net. The labeling time for CNN-corrected segmentation was reduced by more than half compared to that in manual segmentation. Active learning was therefore concluded to be capable of reducing labeling efforts through CNN-corrected segmentation and increase training efficiency by iterative learning with limited data.

Development of a CT imaging phantom of anthromorphic lung using fused deposition modeling 3D printing.

Development of patient-specific CT imaging phantoms with randomly incorporated lesions of various shapes and sizes for calibrating image intensity and validating quantitative measurement software is very challenging. In this investigation, a physical phantom that accurately represents a patient's specific anatomy and the intensity of lung CT images at the voxel level will be fabricated using fused deposition modeling (FDM) 3D printing. Segmentation and modeling of a patient's CT data were performed by an expert and the results were confirmed by a thoracic radiologist with more than 20 years of experience. This facilitated the extraction of the details of the patient's anatomy; various kinds of nodules with different shapes and sizes were randomly added to the modeled lung for evaluating the size-accuracy of the quantification software. To achieve these Hounsfield Units (HU) ranges for the corresponding voxels in acquired CT scans, the infill ratios of FDM 3D printing were controlled. Based on CT scans of the 3D printed phantoms, the measured HU for normal pulmonary parenchyma, ground glass opacity (GGO), and solid nodules were determined to be within target HU ranges. The accuracy of the mean absolute difference and the mean relative difference of nodules were less than 0.55 ±â€Š0.30 mm and 3.72 ±â€Š1.64% (mean difference ±â€Š95 CI), respectively. Patient-specific CT imaging phantoms were designed and manufactured using an FDM printer, which could be applied for the precise calibration of CT intensity and the validation of image quantification software.

Accuracy of a simplified 3D-printed implant surgical guide.

STATEMENT OF PROBLEM: The accuracy of 3D printing technology is essential for clinical applications. However, depending on the 3D printing method, machine, and environment, the accuracy varies even if the same computer-aided design (CAD) model is printed. PURPOSE: The purpose of this in vitro study was to evaluate the differences between the CAD model and the printed parts with a simplified guide designed based on the implant guide and to compare the accuracy among 3 types of 3D printers. MATERIAL AND METHODS: A maxilla and mandible implant guide made of complex anatomic structures is difficult to measure accurately. For accurate measurements, 16 simplified guides were designed based on the maxilla and mandible implant guide. The 16 simplified guides were fabricated by using the following 3 different 3D printer technologies: photopolymer jetting (PolyJet), stereolithography apparatus (SLA), and multijet printing (MJP). Each simplified guide was measured 4 times with digital calipers for 20 linear measurements. The measured simplified guides were compared with the CAD model, and the accuracy of the 3D printers was compared. The mean absolute difference and mean relative difference were calculated, and the Bland-Altman analysis was used to evaluate the limits of agreement between the CAD model and the printed parts. The Wilcoxon signed-rank test was performed to evaluate the significant differences among the 3D printers (α=.05). RESULTS: The mean absolute difference and the mean relative difference between the CAD model and the 3D-printed parts were 0.06 ±0.05 mm (0.46 ±0.51%) for PolyJet, 0.09 ±0.05 mm (0.66 ±0.62%) for SLA, and 0.31 ±0.33 mm (1.11 ±0.70%) for MJP. When the 3D printers were compared, significant differences were found between SLA and MJP (P=.006) and between PolyJet and MJP (P=.001). CONCLUSIONS: When the CAD models and the 3D-printed parts of the simplified implant guides were compared, significant accuracy differences were observed. The PolyJet and SLA 3D printers met the required accuracy for clinical applications in dentistry. The most suitable 3D printer, however, should be selected considering all factors.

MRI-based 3D-printed surgical guides for breast cancer patients who received neoadjuvant chemotherapy.

Magnetic resonance imaging (MRI) is the most accurate technique for evaluating residual tumor after neoadjuvant chemotherapy. However, precise determination of the extent of dispersed residual tumor in the breast following treatment remains a difficult task. We hereby introduce three-dimensional (3D)-printed surgical guides for use in breast cancer patients undergoing breast-conserving surgery after receiving neoadjuvant chemotherapy. We prospectively applied the 3D-printed surgical guides on breast cancer patients who underwent partial breast resection after receiving neoadjuvant chemotherapy. Breasts and tumors were modeled in 3D by using pretreatment magnetic resonance images, and surgical guides were created by using a 3D printer to mark the primary tumor. Out of the five patients who participated in the study, all patients had clear resection margins, and two patients experienced complete pathological remission. There were no recurrences during the median follow-up period of 21.9 months. Thus, our newly-developed 3D-printed surgical guides were useful for accurately marking the extent of breast tumor based on pretreatment magnetic resonance images, which is important for designating the extent of surgery needed in patients who have received neoadjuvant chemotherapy.

Generation of customized orbital implant templates using 3-dimensional printing for orbital wall reconstruction.

OBJECTIVES: To describe and evaluate a novel surgical approach to orbital wall reconstruction that uses three-dimensionally (3D) printed templates to mold a customized orbital implant. METHODS: A review was conducted of 11 consecutive patients who underwent orbital wall reconstruction using 3D-printed customized orbital implant templates. In these procedures, the orbital implant was 3D pressed during surgery and inserted into the fracture site. The outcomes of this approach were analyzed quantitatively by measuring the orbital tissue volumes within the bony orbit using computed tomography. RESULTS: All 11 orbital wall reconstructions (6 orbital floor and 5 medial wall fractures) were successful with no post operative ophthalmic complications. Statistically significant differences were found between the preoperative and post operative orbital tissue volumes for the affected orbit (24.00 ± 1.74 vs 22.31 ± 1.90 cm3; P = 0.003). There was no statistically significant difference found between the tissue volume of the contralateral unaffected orbit and the affected orbit after reconstruction (22.01 ± 1.60 cm3 vs 22.31 ± 1.90 cm3; P = 0.182). CONCLUSION: 3D-printed customized orbital implant templates can be used to press and trim conventional implantable materials with patient-specific contours and sizes for optimal orbital wall reconstruction. It is difficult to design an orbital implant that exactly matches the shape and surface of a blowout fracture site due to the unique 3D structure of the orbit. The traditional surgical method is to visually inspect the fracture site and use eye measurements to cut a two-dimensional orbital implant that corresponds to the anatomical structure of the fracture site. However, implants that do not fit the anatomical structure of a fracture site well can cause complications such as enophthalmos, diplopia and displacement of the implant.

Effect of pannus formation on the prosthetic heart valve: In vitro demonstration using particle image velocimetry.

Although hemodynamic influence of the subprosthetic tissue, termed as pannus, may contribute to prosthetic aortic valve dysfunction, the relationship between pannus extent and hemodynamics in the prosthetic valve has rarely been reported. We investigated the fluid dynamics of pannus formation using in vitro experiments with particle image velocimetry. Subvalvular pannus formation caused substantial changes in prosthetic valve transvalvular peak velocity, transvalvular pressure gradient (TPG) and opening angle. Maximum flow velocity and corresponding TPG were mostly affected by pannus width. When the pannus width was 25% of the valve diameter, pannus formation elevated TPG to >2.5 times higher than that without pannus formation. Opening dysfunction was observed only for a pannus involvement angle of 360°. Although circumferential pannus with an involvement angle of 360° decreased the opening angle of the valve from approximately 82° to 58°, eccentric pannus with an involvement angle of 180° did not induce valve opening dysfunction. The pannus involvement angle largely influenced the velocity flow field at the aortic sinus and corresponding hemodynamic indices, including wall shear stress, principal shear stress and viscous energy loss distributions. Substantial discrepancy between the velocity-based TPG estimation and direct pressure measurements was observed for prosthetic valve flow with pannus formation.

Comparison of Shallow and Deep Learning Methods on Classifying the Regional Pattern of Diffuse Lung Disease.

This study aimed to compare shallow and deep learning of classifying the patterns of interstitial lung diseases (ILDs). Using high-resolution computed tomography images, two experienced radiologists marked 1200 regions of interest (ROIs), in which 600 ROIs were each acquired using a GE or Siemens scanner and each group of 600 ROIs consisted of 100 ROIs for subregions that included normal and five regional pulmonary disease patterns (ground-glass opacity, consolidation, reticular opacity, emphysema, and honeycombing). We employed the convolution neural network (CNN) with six learnable layers that consisted of four convolution layers and two fully connected layers. The classification results were compared with the results classified by a shallow learning of a support vector machine (SVM). The CNN classifier showed significantly better performance for accuracy compared with that of the SVM classifier by 6-9%. As the convolution layer increases, the classification accuracy of the CNN showed better performance from 81.27 to 95.12%. Especially in the cases showing pathological ambiguity such as between normal and emphysema cases or between honeycombing and reticular opacity cases, the increment of the convolution layer greatly drops the misclassification rate between each case. Conclusively, the CNN classifier showed significantly greater accuracy than the SVM classifier, and the results implied structural characteristics that are inherent to the specific ILD patterns.