Quantifying the Efficacy of Magnetic Nanoparticles for MRI and Hyperthermia Applications via Machine Learning Methods.

Magnetic nanoparticles are a prospective class of materials for use in biomedicine as agents for magnetic resonance imagining (MRI) and hyperthermia treatment. However, synthesis of nanoparticles with high efficacy is resource-intensive experimental work. In turn, the use of machine learning (ML) methods is becoming useful in materials design and serves as a great approach to designing nanomagnets for biomedicine. In this work, for the first time, an ML-based approach is developed for the prediction of main parameters of material efficacy, i.e., specific absorption rate (SAR) for hyperthermia and r1 /r2 relaxivities in MRI, with parameters of nanoparticles as well as experimental conditions as descriptors. For that, a unique database with more than 980 magnetic nanoparticles collected from scientific articles is assembled. Using this data, several tree-based ensemble models are trained to predict SAR, r1 and r2 relaxivity. After hyperparameter optimization, models reach performances of R2 = 0.86, R2 = 0.78, and R2 = 0.75, respectively. Testing the models on samples unseen during the training shows no performance drops. Finally, DiMag, an open access resource created to guide synthesis of novel nanosized magnets for MRI and hyperthermia treatment with machine learning and boost development of new biomedical agents, is developed.

The emotional face of anorexia nervosa: The neural correlates of emotional processing.

Social-emotional processing difficulties have been reported in Anorexia Nervosa (AN), yet the neural correlates remain unclear. Previous neuroimaging work is sparse and has not used functional connectivity paradigms to more fully explore the neural correlates of emotional difficulties. Fifty-seven acutely unwell AN (AAN) women, 60 weight-recovered AN (WR) women and 69 healthy control (HC) women categorised the gender of a series of emotional faces while undergoing Functional Magnetic Resonance Imaging. The mean age of the AAN group was 19.40 (2.83), WR 18.37 (3.59) and HC 19.37 (3.36). A whole brain and psychophysical interaction connectivity approach was used. Parameter estimates from significant clusters were extracted and correlated with clinical symptoms. Whilst no group level differences in whole brain activation were demonstrated, significant group level functional connectivity differences emerged. WR participants showed increased connectivity between the bilateral occipital face area and the cingulate, precentral gyri, superior, middle, medial and inferior frontal gyri compared to AAN and HC when viewing happy valenced faces. Eating disorder symptoms and parameter estimates were positively correlated. Our findings characterise the neural basis of social-emotional processing in a large sample of individuals with AN.

Comparison of clinical and magnetic resonance imagining data of patients with temporomandibular disorders.

BACKGROUND: There are important criteria in the diagnosis of temporomandibular disorders (TMDs). These become significant if supported by magnetic resonance imaging (MRI). Otherwise, these findings alone may not be sufficient to diagnose TMD. AIM: This study compared the relationship between clinical findings indicated by patient and physician and MRI results in the diagnosis of TMD. MATERIALS AND METHODS: Clinical examinations were performed in patients suspected of TMD for pain, difficulty in mouth opening, masticatory muscle tenderness, deviation (during mouth opening), normal mouth opening, and presence of bruxism. The MRI findings of the patients were compared with the clinical examinations. RESULTS: MRI and clinical examination data of 136 patients were examined. The results showed significant correlations between deviation, normal mouth opening, and MRI results of TMD (P < 0.05). No correlation was found between age groups and clinical findings of TMD. TMJ was determined in normal limits in 61% of MRI results. CONCLUSIONS: Except for deviation and normal mouth opening, complaints and clinical findings determined by the clinicians do not support TMD. This may be due to the subjective nature of the clinical findings, and MRI results are needed for precise results.

Investigating heartbeat-related in-plane motion and stress levels induced at the aortic root.

BACKGROUND: The axial motion of aortic root (AR) due to ventricular traction was previously suggested to contribute to ascending aorta (AA) dissection by increasing its longitudinal stress, but AR in-plane motion effects on stresses have never been studied. The objective is to investigate the contribution of AR in-plane motion to AA stress levels. METHODS: The AR in-plane motion was assessed on magnetic resonance imagining data from 25 healthy volunteers as the movement of the AA section centroid. The measured movement was prescribed to the proximal AA end of an aortic finite element model to investigate its influences on aortic stresses. The finite element model was developed from a patient-specific geometry using LS-DYNA solver and validated against the aortic distensibility. Fluid-structure interaction (FSI) approach was also used to simulate blood hydrodynamic effects on aortic dilation and stresses. RESULTS: The AR in-plane motion was 5.5 ± 1.7 mm with the components of 3.1 ± 1.5 mm along the direction of proximal descending aorta (PDA) to AA centroid and 3.0 ± 1.3 mm perpendicularly under the PDA reference system. The AR axial motion elevated the longitudinal stress of proximal AA by 40% while the corresponding increase due to in-plane motion was always below 5%. The stresses at proximal AA resulted approximately 7% less in FSI simulation with blood flow. CONCLUSIONS: The AR in-plane motion was comparable with the magnitude of axial motion. Neither axial nor in-plane motion could directly lead to AA dissection. It is necessary to consider the heterogeneous pressures related to blood hydrodynamics when studying aortic wall stress levels.

Gadopentatic acid affects in vitro proliferation and doxorubicin response in human breast adenocarcinoma cells.

Contrasting agents (CAs) that are administered to patients during magnetic resonance imaging to facilitate tumor identification are generally considered harmless. However, gadolinium (Gd) based contrast agents can be retained in the body, inflicting specific cell line cytotoxicity. We investigate the effect of Gadopentatic acid (Gd-DTPA) on human breast adenocarcinoma MCF-7 cells. These cells exhibit a toggle switch response: exposure to 0.1 and 1 mM concentrations of Gd-DTPA enhances proliferation, which is hindered at a higher 10 mM concentration. Proliferation is enhanced when cells transition to 3D morphologies in post confluent conditions. The proliferation dependence on the concentration of CA is absent for Hs 578T and MDA-MB-231 triple negative cell lines. MCF-7 cells reveal a double toggle switch related to the expression of VEGF, which goes through high-low-high downregulation when cells are exposed to 0.1, 1, and 10 mM Gd-DTPA, respectively. Finally, doxorubicin drug response is assessed, which also reveals a double toggle switch behavior, where drug cytotoxicity exhibits a nonlinear dependence on the CA concentration. A toggle switch in cell characteristics that are exposed to 1 mM of Gd-DTPA amplifies the importance of this threshold, affecting several cell behaviors if surpassed. This work emphasizes the important effects that CAs can have on cells, specifically Gd-DTPA on MCF-7 cells, and the implications for cell growth and drug response during clinical and synthetic biology procedures.

Spinal multiparametric MRI and DEXA changes over time in men with prostate cancer treated with androgen deprivation therapy: a potential imaging biomarker of treatment toxicity.

OBJECTIVES: To explore changes in bone mineral density (BMD) measured by DEXA and MRS fat fraction (FF), Dixon FF, and ADC in lower spinal vertebral bodies in men with prostate cancer treated with androgen deprivation therapy (ADT). METHODS: Twenty-eight men were enrolled onto a clinical trial. All received ADT. DEXA imaging was performed at baseline and 12 months. L-spine MRI was done at baseline and 6 months. RESULTS: The number of patients who underwent DEXA, Dixon, ADC, and MRS at baseline/follow-up were 28/27, 28/26, 28/26, and 22/20. An increase in FF was observed from T11 to S2 (average 1 %/vertebra). There was a positive correlation between baseline MRS FF and Dixon FF (r = 0.85, p < 0.0001) and a negative correlation between MRS FF and ADC (r = -0.56, p = 0.036). Over 6 months, MRS FF increased by a median of 25 % in relative values (p = 0.0003), Dixon FF increased (p < 0.0001) and ADC values decreased (p = 0.0014). Men with >5 % BMD loss after 1 year had triple the percentage increase in MRS FF at 6 months (61.1 % vs. 20.9 %, p = 0.19). CONCLUSIONS: Changes are observed on L-spine MRI after 6 months of ADT. Further investigation is warranted of MRS change as a potential predictive biomarker for later BMD loss. KEY POINTS: • Spinal marrow fat fraction increases after 6 months of androgen deprivation therapy. • More inferior vertebral bodies tend to have higher fat fractions. • MRS fat fraction changes were associated with later changes in DEXA BMD.

Use of trimetasphere metallofullerene MRI contrast agent for the non-invasive longitudinal tracking of stem cells in the lung.

Magnetic Resonance Imaging (MRI) is a commonly used, non-invasive imaging technique that provides visualization of soft tissues with high spatial resolution. In both a research and clinical setting, the major challenge has been identifying a non-invasive and safe method for longitudinal tracking of delivered cells in vivo. The labeling and tracking of contrast agent labeled cells using MRI has the potential to fulfill this need. Contrast agents are often used to enhance the image contrast between the tissue of interest and surrounding tissues with MRI. The most commonly used MRI contrast agents contain Gd(III) ions. However, Gd(III) ions are highly toxic in their ionic form, as they tend to accumulate in the liver, spleen, kidney and bones and block calcium channels. Endohedral metallofullerenes such as trimetallic nitride endohedral metallofullerenes (Trimetasphere®) are one unique class of fullerene molecules where a Gd3N cluster is encapsulated inside a C80 carbon cage referred to as Gd3N@C80. These endohedral metallofullerenes have several advantages over small chelated Gd(III) complexes such as increased stability of the Gd(III) ion, minimal toxic effects, high solubility in water and high proton relativity. In this study, we describe the evaluation of gadolinium-based Trimetasphere® positive contrast agent for the ​in vitro labeling and in vivo tracking of human amniotic fluid-derived stem cells within lung tissue. In addition, we conducted a 'proof-of-concept' experiment demonstrating that this methodology can be used to track the homing of stem cells to injured lung tissue and provide longitudinal analysis of cell localization over an extended time course.

Tuning the Fe-Gd nanoparticles co-functionalized mesoporous carbon from sphere to nanobowl for advanced bioapplications.

Studies on the function-integrated nanocomposites with well-tuned morphologies have received considerable interest. Here, we reported the preparation of mesoporous carbon nanobowl integrated with stoichiometric γ-Fe2O3 and GdPO4 nanoparticles (Fe-Gd/MCN-B) for morphological advantage exploration. Followed by (i) emulsion-induced interface anisotropic assembly of polydopamine, (ii) solvent evaporation-induced sorption of Wells-Dawson-like heterometallic cluster of {Fe6Gd6P6} and (iii) temperature-programmed carbonization, Fe-Gd/MCN-B with the size around 200 nm was isolated. Our in-vitro studies revealed that Fe-Gd/MCN-B showed a 63.0 % amplified photoacoustic (PA) signal intensity as compared with its nanospherical analogue of Fe-Gd/MCN-S owing to the enhanced light harvesting and photothermal conversion on the interface of its nanobowl morphology. Furthermore, the combined magnetic resonance (MR) imagining, drug delivery and photothermal treatment efficacy in Fe-Gd/MCN-B were also validated in-vitro. These results demonstrated that the delicate design of the morphology of function-integrated nanocomposites is an available way for enhanced imaging performance.

Delta radiomic patterns on serial bi-parametric MRI are associated with pathologic upgrading in prostate cancer patients on active surveillance: preliminary findings.

Objective: The aim of this study was to quantify radiomic changes in prostate cancer (PCa) progression on serial MRI among patients on active surveillance (AS) and evaluate their association with pathologic progression on biopsy. Methods: This retrospective study comprised N = 121 biopsy-proven PCa patients on AS at a single institution, of whom N = 50 at baseline conformed to the inclusion criteria. ISUP Gleason Grade Groups (GGG) were obtained from 12-core TRUS-guided systematic biopsies at baseline and follow-up. A biopsy upgrade (AS+) was defined as an increase in GGG (or in number of positive cores) and no upgrade (AS-) was defined when GGG remained the same during a median period of 18 months. Of N = 50 patients at baseline, N = 30 had MRI scans available at follow-up (median interval = 18 months) and were included for delta radiomic analysis. A total of 252 radiomic features were extracted from the PCa region of interest identified by board-certified radiologists on 3T bi-parametric MRI [T2-weighted (T2W) and apparent diffusion coefficient (ADC)]. Delta radiomic features were computed as the difference of radiomic feature between baseline and follow-up scans. The association of AS+ with age, prostate-specific antigen (PSA), Prostate Imaging Reporting and Data System (PIRADS v2.1) score, and tumor size was evaluated at baseline and follow-up. Various prediction models were built using random forest (RF) classifier within a threefold cross-validation framework leveraging baseline radiomics (Cbr), baseline radiomics + baseline clinical (Cbrbcl), delta radiomics (CΔr), delta radiomics + baseline clinical (CΔrbcl), and delta radiomics + delta clinical (CΔrΔcl). Results: An AUC of 0.64 ± 0.09 was obtained for Cbr, which increased to 0.70 ± 0.18 with the integration of clinical variables (Cbrbcl). CΔr yielded an AUC of 0.74 ± 0.15. Integrating delta radiomics with baseline clinical variables yielded an AUC of 0.77 ± 0.23. CΔrΔclresulted in the best AUC of 0.84 ± 0.20 (p < 0.05) among all combinations. Conclusion: Our preliminary findings suggest that delta radiomics were more strongly associated with upgrade events compared to PIRADS and other clinical variables. Delta radiomics on serial MRI in combination with changes in clinical variables (PSA and tumor volume) between baseline and follow-up showed the strongest association with biopsy upgrade in PCa patients on AS. Further independent multi-site validation of these preliminary findings is warranted.

Lifetime physical activity is associated with gut bacteria and brain health in people with multiple sclerosis: Focus on physical activity intensity.

BACKGROUND: Physical activity can improve brain health in people with multiple sclerosis (PwMS). One of the underlying mechanisms can be the modulation of gut bacteria. The association of different intensity of physical activity in a lifetime; and brain volume, lesion volume, and number, and gut bacteria counts were investigated in the current study. METHODS: Forty-five PwMS were recruited, and magnetic resonance imagining was used to evaluate brain volume, lesion volume, and number. Also, stool samples were taken for evaluation faecalibacterium prausnitzii, akkermansia muciniphila, prevotella, and bacteroides count. Moreover, lifetime physical activity was assessed using the adapted version of the historical activity questionnaire. RESULTS: Data revealed a significant association of physical activity with brain volume (r = 0.41), lesion volume (r=-0.35), lesion number (r=-0.37), akkermansia muciniphila (r=-0.34), prevotella (r = 0.52) and bacteroides (r=-0.32) count (p<0.05). Moderate-intensity of physical activity was associated with brain volume (r = 0.33), lesion volume (r=-0.38), prevotella (r = 0.35) and bacteroides (r=-0.40) count (p<0.05). Moreover, vigorous-intensity of physical activity was associated with brain volume (r = 0.38), lesion number (r=-0.39), akkermansia muciniphila (r=-0.30) and prevotella (r = 0.56) count (p<0.05). CONCLUSION: Our results suggest that lifetime physical activity is associated with brain health and gut bacteria count in PwMS. Additionally, the heterogeneity of the association of the physical activity intensities with the studied variables indicates the importance of using different intensities of physical activity to greater benefit from physical activity.

Experimental study on the accuracy of non-invasive temperature measurement by magnetic resonance in microwave ablation.

Aims: This study aimed to explore the accuracy of non-invasive temperature measurement based on proton resonance frequency (PRF) phase subtraction in microwave ablation (MWA). Methods and Material: The signal change of the agar phantom during the ablation process was monitored by the gradient echo sequence under 1.5 T superconducting magnetic resonance imagining (MRI), and the temperature change was converted by the phase subtraction method of the PRF, which was compared with the temperature measured using an optical fiber. Statistical Analysis Used: SPSS software version 22.0 was used for data processing, and the independent sample t-test was used for comparative analysis. P < 0.05 indicated statistical significance. Results: The maximum error between the MRI temperature measurement and the standard value was 3.61°C, whereas the minimum and average errors were 0.01°C and 1.19°C ± 0.78°C, respectively. Conclusions: The temperature measurement technology, which is based on the PRF phase method, has good accuracy in MRI-guided MWA.

The Link of Pancreatic Iron with Glucose Metabolism and Cardiac Iron in Thalassemia Intermedia: A Large, Multicenter Observational Study.

In thalassemia major, pancreatic iron was demonstrated as a powerful predictor not only for the alterations of glucose metabolism but also for cardiac iron, fibrosis, and complications, supporting a profound link between pancreatic iron and heart disease. We determined for the first time the prevalence of pancreatic iron overload (IO) in thalassemia intermedia (TI) and systematically explored the link between pancreas T2* values and glucose metabolism and cardiac outcomes. We considered 221 beta-TI patients (53.2% females, 42.95 ± 13.74 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia project. Magnetic Resonance Imaging was used to quantify IO (T2* technique) and biventricular function and to detect replacement myocardial fibrosis. The glucose metabolism was assessed by the oral glucose tolerance test (OGTT). Pancreatic IO was more frequent in regularly transfused (N = 145) than in nontransfused patients (67.6% vs. 31.6%; p < 0.0001). In the regular transfused group, splenectomy and hepatitis C virus infection were both associated with high pancreatic siderosis. Patients with normal glucose metabolism showed significantly higher global pancreas T2* values than patients with altered OGTT. A pancreas T2* < 17.9 ms predicted an abnormal OGTT. A normal pancreas T2* value showed a 100% negative predictive value for cardiac iron. Pancreas T2* values were not associated to biventricular function, replacement myocardial fibrosis, or cardiac complications. Our findings suggest that in the presence of pancreatic IO, it would be prudent to initiate or intensify iron chelation therapy to prospectively prevent both disturbances of glucose metabolism and cardiac iron accumulation.

Multi-modal Mapping of the Face Selective Ventral Temporal Cortex-A Group Study With Clinical Implications for ECS, ECoG, and fMRI.

Face recognition is impaired in patients with prosopagnosia, which may occur as a side effect of neurosurgical procedures. Face selective regions on the ventral temporal cortex have been localized with electrical cortical stimulation (ECS), electrocorticography (ECoG), and functional magnetic resonance imagining (fMRI). This is the first group study using within-patient comparisons to validate face selective regions mapping, utilizing the aforementioned modalities. Five patients underwent surgical treatment of intractable epilepsy and joined the study. Subdural grid electrodes were implanted on their ventral temporal cortices to localize seizure foci and face selective regions as part of the functional mapping protocol. Face selective regions were identified in all patients with fMRI, four patients with ECoG, and two patients with ECS. From 177 tested electrode locations in the region of interest (ROI), which is defined by the fusiform gyrus and the inferior temporal gyrus, 54 face locations were identified by at least one modality in all patients. fMRI mapping showed the highest detection rate, revealing 70.4% for face selective locations, whereas ECoG and ECS identified 64.8 and 31.5%, respectively. Thus, 28 face locations were co-localized by at least two modalities, with detection rates of 89.3% for fMRI, 85.7% for ECoG and 53.6 % for ECS. All five patients had no face recognition deficits after surgery, even though five of the face selective locations, one obtained by ECoG and the other four by fMRI, were within 10 mm to the resected volumes. Moreover, fMRI included a quite large volume artifact on the ventral temporal cortex in the ROI from the anatomical structures of the temporal base. In conclusion, ECS was not sensitive in several patients, whereas ECoG and fMRI even showed activation within 10 mm to the resected volumes. Considering the potential signal drop-out in fMRI makes ECoG the most reliable tool to identify face selective locations in this study. A multimodal approach can improve the specificity of ECoG and fMRI, while simultaneously minimizing the number of required ECS sessions. Hence, all modalities should be considered in a clinical mapping protocol entailing combined results of co-localized face selective locations.

Value of systematic sampling in an mp-MRI targeted prostate biopsy strategy.

The clinical utility of systematic prostate biopsy in addition to multi-parametric magnetic resonance imagining (mp-MRI) targeted biopsy pathways remains unclear. Despite radiological advancements in mp-MRI and utilisation of international standardised reporting systems (i.e., PI-RADS, LIKERT), undetected clinically significant prostate cancer (csPCa) on imaging persists. This has prevented the widespread adoption of an exclusively targeted biopsy approach. The current evidence on csPCa cancer detection rates in mp-MRI targeted alone and combined with a non-targeted systematic sampling is presented. Arguments for and against routine limited systematic sampling as an adjunct to an mp-MRI targeted biopsy are discussed. Our review will report the clinical utility of a combined sampling strategy on csPCa detection rate. The available evidence suggests that we are yet to reach a stage where non-targeted systematic prostate biopsy can be routinely omitted in mp-MRI targeted prostate biopsy pathways. Research should focus on improving the accuracy of mp-MRI, prostate biopsy techniques, and in identifying those men that will most benefit from a combined prostate biopsy. Such strategies may help future urologists reduce the burden of non-targeted cores in modern mp-MRI prostate biopsy pathways.

Synthesis and characterization of bacteriochlorin loaded magnetic nanoparticles (MNP) for personalized MRI guided photosensitizers delivery to tumor.

HYPOTHESIS: Hydrophobic bacteriochlorin based photosensitizer (PS) can be effectively immobilized on MNP covered by human serum albumin (HSA). PS loading into MNP protein shell allows solubilizing PS in water solution without altering its photodynamic activity. MNP@PS can serve as diagnostic tool for tracking PS delivery to tumor tissues by MRI. EXPERIMENTS: Immobilization on MNP-HSA-PEG was performed by adding PS solution in organic solvents with further purification. MNP@PS were characterized by DLS, HAADF STEM and AFM. Absorbance and fluorescence measurements were used to assess PS photophysical properties before and after immobilization. MNP@PS internalization into CT26 cells was investigated by confocal microscopy in vitro and MRI/IVIS were used for tracking MNP@PS delivery to tumors in vivo. FINDINGS: MNP@PS complexes were stable in water solution and retained PS photophysical activity. The length of side chain affected MNP@PS size, loading capacity and cell internalization. In vitro testing demonstrated MNP@PS delivery to cancer cells followed by photoinduced toxicity. In vivo studies confirmed that as-synthetized complexes can be used for MRI tracking over drug accumulation in tumors.

The Utility of Magnetic Resonance Imaging-compatible Pacemakers in Neurosurgical Patients.

Artificial implantable pacemakers have long been a challenge to neurosurgeons seeking to perform advanced diagnostic imaging on their patients. Unfortunately, while the use of implantable pacemakers has been a life-saving advance for those with cardiac arrhythmias, they also often prevent these patients from undergoing magnetic resonance imaging (MRI). There have been multiple reported cases of pacemaker failure in the context of MRI use. Recent technological advances, however, have allowed the development of pacemakers that are not affected by the MRI scanner. Similar technology has also been applied to the development of MRI-compatible spinal cord stimulators and other neurostimulation devices. In this paper, we discuss four specific neurosurgical cases where the use of MRI was critical for diagnostic and therapeutic decision-making. Current non-MRI-compatible pacemakers were exchanged for MRI-compatible pacemaker technology with some associated cost and risk. The diagnostic cranial and spinal MRIs subsequently obtained were critical for forging the ensuing neurosurgical care. Based on these cases, we extrapolate the importance of MRI-compatible pacemakers to society at large and advocate for the use of such devices in all patients going forward.

Magnetic Resonance Imaging Volumetry of Primary Nasopharyngeal Cancer in Patients Treated with Induction Gemcitabine and Cisplatin Followed by Concurrent Cisplatin and Volumetric Modulated Arc Therapy.

Introduction The addition of induction chemotherapy (IC) to the standard concurrent chemoradiotherapy (CCRT) is under consideration in locally advanced nasopharyngeal carcinoma (LANPC). To-date, no studies have reported primary gross tumour volume (GTVp) changes using gemcitabine and cisplatin as the IC phase in LANPC. We investigated the timing and magnitude of GTVp response throughout sequential gemcitabine and cisplatin IC and CCRT for LANPC. Toxicity and tumour control probability (TCP) analyses are also presented Methods Ten patients with LANPC underwent sequential IC and CCRT between 2011 and 2015. All patients had magnetic resonance imaging (MRI) at three time points: before IC (MRI0), after IC (MRI1), and three months after CCRT (MRI3). Five of the 10 patients had an additional MRI four to five weeks into CCRT (MRI2). GTVp contours were delineated retrospectively using contrast-enhanced MRIs, and each GTVp underwent secondary review by a neuroradiologist. Acute toxicities were graded retrospectively via chart review based on the National Cancer Institute Common Terminology for Adverse Events version 4.0 (NCI CTCAE v4.0). Results Mean GTVp reduction between MRI0 - MRI1 was from 68 cc to 47 cc and from 47 cc to 9 cc between MRI1 - MRI3. In patients with MRI2, the mean GTVp reduction between MRI1 - MRI2 was from 57 cc to 32 cc. Tumour control probability estimates increased by 0.11 after IC. Patients tolerated the treatment well with one Grade IV toxicity event. Conclusion The observed GTVp response and improved tumor control probability support further investigation into the use of IC in LANPC.

Iron Oxide Nanoparticles: Innovative Tool in Cancer Diagnosis and Therapy.

Although cancer is one of the most dangerous and the second most lethal disease in the world, current therapy including surgery, chemotherapy, radiotherapy, etc., is highly insufficient not in the view of therapy success rate or the amount of side effects. Accordingly, procedures with better outcomes are highly desirable. Iron oxide nanoparticles (IONPs) present an innovative tool-ideal for innovation and implementation into practice. This review is focused on summarizing some well-known facts about pharmacokinetics, toxicity, and the types of IONPs, and furthermore, provides a survey of their use in cancer diagnosis and therapy.

Solitary rectal ulcer syndrome complicating sessile serrated adenoma/polyps: A case report and review of literature.

Solitary rectal ulcer syndrome (SRUS) is a rare benign condition, which can mimic many other diseases because of their similarities in clinical, endoscopic and histological features. Sessile serrated adenoma/polyp (SSA/p) is a premalignant lesion in the colon and rectum. The misdiagnosis of SSA/p in SRUS patients has been noted, but the case of SRUS arising secondarily to SSA/p has been rarely reported. We herein report the case of a 59-year-old man who presented with an ulcerative nodular lesion in the rectum, accompanied by the symptoms of blood and mucus in the feces, diarrhea and constipation. Magnetic resonance imagining revealed thickening of the rectal mucosa-submucosa. Histologically, the lesion was characterized by the hyperplastic lamina propria and diffusely serrated crypts. Further immunohistochemical staining showed the loss of HES1 and MLH1 expression in the epithelial cells in the serrated area. The patient with SRUS had histological changes of SSA/p, suggesting a potential of tumor transformation in certain cases. SRUS uncommonly accompanied by serrated lesions should at least be considered by pathologists and clinicians.

A novel in vivo large animal model of lumbar spinal joint degeneration.

BACKGROUND CONTEXT: Degenerative disc disease (DDD) is a common, widespread socioeconomic problem. Appropriate large animal models of DDD are required for improved understanding and to serve as preclinical test beds for therapeutic strategies. PURPOSE: To evaluate the effects of short and medium duration immobilization on the sheep lumbar intervertebral disc (IVD) and facet joints (FJs), and to establish a large animal model for DDD research. STUDY DESIGN: An in vivo sheep model evaluating the effect of short- and medium-term immobilization on disc degeneration. METHODS: Eighteen sheep were equally randomized into three groups: short-term (6-week) immobilization (n=6), medium-term (26-week) immobilization (n=6), and control (no surgery) (n=6). Immobilization of L3-L4 was achieved with pedicle screw and rod implantation, the IVD was kept intact, and the annulus and end plates were not disrupted. The IVD and FJs were assessed with planar radiography, computerized tomography (CT), magnetic resonance imaging (MRI), pure moment biomechanical testing, and histologic analysis. RESULTS: Disc height was reduced for 6- and 26-week immobilization groups. The MRI and histologic analysis demonstrated significant disc degeneration for both immobilized groups compared with control, but no statistical difference was detected between short- and medium-term duration. Progressive degenerative changes in FJs were observed with micro-CT and histologic end points. Immobilization significantly reduced lateral bending and flexion-extension range of motion. CONCLUSIONS: The mechanical environment set up by immobilization alone is capable of inducing lumbar disc degeneration at both 6 and 26 weeks in sheep. Longer duration immobilization did not advance disc degeneration process beyond of that found with short duration. The present model produces a degenerative disc with intact annulus and without acute injury, more closely representing the scenario common in human disc degeneration. This provides a suitable large animal in vivo model for the evaluation of the new therapies for disc degeneration. Further studies would do well to examine the effect of remobilization after immobilization in this model.