A feasibility study of several 3D printing methods for applications in epilepsy surgery.

OBJECTIVE: To describe the process of three-dimensional printing in epilepsy surgery using three different methods: low-force stereolithography (SLA), filament deposition modeling (FDM), and Polyjet Stratasys, while comparing them in terms of printing efficiency, cost, and clinical utility. MRI and CT images of patient anatomy have been limited to review in the two-dimensional plane, which provides only partial representation of intricate intracranial structures. There has been growing interest in 3D printing of physical models of this complex anatomy to be used as an educational tool and for surgical visualization. One specific application is in epilepsy surgery where there are challenges in visualizing complex intracranial anatomy in relation to implanted surgical tools. METHODS: MRI and CT data from patients with refractory epilepsy from a single center that underwent surgery are converted into 3D volumes, or stereolithography files. These were then printed using three popular 3D printing methods: SLA, FDM, and Polyjet. Faculty were surveyed on the impact of 3D modeling on the surgical planning process. RESULTS: All three methods generated physical models with an increasing degree of resolution, transparency, and clinical utility directly related to cost of production and accurate representation of anatomy. Polyjet models were the most transparent and clearly represented intricate implanted electrodes but had the highest associated cost. FDM produced relatively inexpensive models that, however, were nearly completely opaque, limiting clinical utility. SLA produced economical and highly transparent models but was limited by single material capacity. SIGNIFICANCE: Three-dimensional printing of patient-specific anatomy is feasible with a variety of printing methods. The clinical utility of lower-cost methods is limited by model transparency and lack of multi-material overlay respectively. Polyjet successfully generated transparent models with high resolution of internal structures but is cost-prohibitive. Further research needs to be done to explore cost-saving methods of modeling.

Excitation of a Single Compound by Light and Ultrasound Enhanced the Long-Term Cure of Mice Bearing Prostate Tumors.

Current treatment for prostate cancer is dependent on the stages of the cancer, recurrence, and genetic factors. Treatment varies from active surveillance or watchful waiting to prostatectomy, chemotherapy, and radiation therapy in combination or alone. Although radical prostate cancer therapy reduces the advancement of the disease and its mortality, the increased disease treatment associated morbidity, erectile dysfunction, and incontinence affect the quality of life of cancer survivors. To overcome these problems, photodynamic therapy (PDT) has previously been investigated using PhotofrinTM as a photosensitizer (PS). However, Photofrin-PDT has shown limitations in treating prostate cancer due to its limited tumor-specificity and the depth of light penetration at 630 nm (the longest wavelength absorption of PhotofrinTM). The results presented herein show that this limitation can be solved by using a near infrared (NIR) compound as a photosensitizer (PS) for PDT and the same agent also acts as a sonosensitizer for SDT (using ultrasound to activate the compound). Compared to light, ultrasound has a stronger penetration ability in biological tissues. Exposing the PS (or sonosensitizer) to ultrasound (US) initiates an electron-transfer process with a biological substrate to form radicals and radical ions (type I reaction). In contrast, exposure of the PS to light (PDT) generates singlet oxygen (type II reaction). Therefore, the reactive oxygen species (ROS) produced by SDT and PDT follow two distinct pathways, i.e., type I (oxygen independent) and type II (oxygen dependent), respectively, and results in significantly enhanced destruction of tumor cells. The preliminary in vitro and in vivo results in a PC3 cell line and tumor model indicate that the tumor specificality of the therapeutic agent(s) can be increased by targeting galectin-1 and galectin-3, known for their overexpression in prostate cancer.

Deep learning-based prediction of rib fracture presence in frontal radiographs of children under two years of age: a proof-of-concept study.

OBJECTIVE: In this proof-of-concept study, we aimed to develop deep-learning-based classifiers to identify rib fractures on frontal chest radiographs in children under 2 years of age. METHODS: This retrospective study included 1311 frontal chest radiographs (radiographs with rib fractures, n = 653) from 1231 unique patients (median age: 4 m). Patients with more than one radiograph were included only in the training set. A binary classification was performed to identify the presence or absence of rib fractures using transfer learning and Resnet-50 and DenseNet-121 architectures. The area under the receiver operating characteristic curve (AUC-ROC) was reported. Gradient-weighted class activation mapping was used to highlight the region most relevant to the deep learning models' predictions. RESULTS: On the validation set, the ResNet-50 and DenseNet-121 models obtained an AUC-ROC of 0.89 and 0.88, respectively. On the test set, the ResNet-50 model demonstrated an AUC-ROC of 0.84 with a sensitivity of 81% and specificity of 70%. The DenseNet-50 model obtained an AUC of 0.82 with 72% sensitivity and 79% specificity. CONCLUSION: In this proof-of-concept study, a deep learning-based approach enabled the automatic detection of rib fractures in chest radiographs of young children with performances comparable to pediatric radiologists. Further evaluation of this approach on large multi-institutional data sets is needed to assess the generalizability of our results. ADVANCES IN KNOWLEDGE: In this proof-of-concept study, a deep learning-based approach performed well in identifying chest radiographs with rib fractures. These findings provide further impetus to develop deep learning algorithms for identifying rib fractures in children, especially those with suspected physical abuse or non-accidental trauma.

Impact of mono- and di-ß-galactose moieties in in vitro / in vivo anticancer efficacy of pyropheophorbide-carbohydrate conjugates by photodynamic therapy.

To investigate the impact of mono- and di-ß-galactose moieties in tumor uptake and photodynamic therapy (PDT) efficacy, HPPH [3-(1'-hexyloxy)ethyl-3-devinylpyropheophorobide-a], the meso pyropheophorbide-a [3-ethyl-3-devinyl-pyropheophorbide-a], and the corresponding 20-benzoic acid analogs were used as starting materials. Reaction of the intermediates containing one or two carboxylic acid functionalities with 1-aminogalactose afforded the desired 172- or 20(4')- mono- and 172, 20(4')-di galactose conjugated photosensitizers (PSs) with and without a carboxylic acid group. The overall lipophilicity caused by the presence of galactose in combination with either an ethyl or (1'-hexyloxy)ethyl side chain at position-3 of the macrocycle made a significant difference in in vitro uptake by tumor cells and photoreaction upon light exposure. Interestingly, among the PSs investigated, compared to HPPH 1 the carbohydrate conjugates 2 and 11 in which ß-galactose moieties are conjugated at positions 172 and 20(4') of meso-pyro pheophorbide-a showed similar in vitro efficacy in FaDu cell lines, but in SCID mice bearing FaDu tumors (head & neck) Ps 11 gave significantly improved long-term tumor cure.

Prenatal Environmental Metal Exposure and Preterm Birth: A Scoping Review.

Preterm birth (PTB) and its complications are the leading causes of under-five year old child deaths, accounting worldwide for an estimated one million deaths annually. The etiology of PTB is complex and multifactorial. Exposures to environmental metals or metalloids are pervasive and prenatal exposures to them are considered important in the etiology of PTB. We conducted a scoping review to determine the extent of prenatal exposures to four metals/metalloids (lead, mercury, cadmium and arsenic) and their association with PTB. We reviewed original research studies published in PubMed, Embase, the Cochrane Library, Scopus, POPLINE and the WHO regional indexes from 2000 to 2019; 36 articles were retained for full text review. We documented a higher incidence of PTB with lead and cadmium exposures. The findings for mercury and arsenic exposures were inconclusive. Metal-induced oxidative stress in the placenta, epigenetic modification, inflammation, and endocrine disruptions are the most common pathways through which heavy metals and metalloids affect placental functions leading to PTB. Most of the studies were from the high-income countries, reflecting the need for additional data from low-middle-income countries, where PTB rates are higher and prenatal exposure to metals are likely to be just as high, if not higher.