Diagnosis and management of occult non-missile penetrating brain injury.

Penetrating brain injury (PBI) is a subtype of traumatic brain injury (TBI) that has been steadily increasing in prevalence and causing significant mortality in trauma patients. In an emergent setting, it is important to determine the mechanism of injury and decide whether a PBI or a blunt TBI has occurred in order to guide diagnostic imaging and subsequent treatment. In cases where a PBI has been likely or has occurred, it is important to initiate treatment expeditiously as rapid interventions have been shown to lead to better outcomes. However, in cases of unwitnessed pediatric trauma, it can be difficult to ascertain the specific method of injury due to a lack of reliable sources. In such cases of unwitnessed trauma, PBI should be included in the differential of any orbitocranial injury. In this series, we present two cases of unwitnessed pediatric orbitocranial injury that highlight the importance of gathering a detailed history, obtaining appropriate imaging studies, and using physician intuition.

Site matters: Image-guided percutaneous sampling of intervertebral disc results in increased positive diagnostic yield in spondylodiscitis.

Spondylodiscitis is a common referral to spinal on call services. Identification of the causative organism is vital in order to dictate the appropriate antibiotic treatment. In this context, the surgical and interventional radiology team is often asked to perform a diagnostic biopsy. The aim of the present study was to assess whether the sampling location affects the diagnostic yield. Our results suggest that the overall positive diagnostic yield was 35%. When disc material was included in the sample the diagnostic yield significantly improved to 47%. Bone sampling alone had a positive yield of 15%. Age, pre-biopsy CRP, pre-biopsy use of antibiotics did not seem to affect the likelihood of obtaining a positive yield. These results suggests that when performing image guided biopsies for suspected cases of spondylodiscitis the inclusion of disc material is important.

A model-based approach to assess reproducibility for large-scale high-throughput MRI-based studies.

Magnetic Resonance Imaging (MRI) technology has been increasingly used in neuroscience studies. Reproducibility of statistically significant findings generated by MRI-based studies, especially association studies (phenotype vs. MRI metric) and task-induced brain activation, has been recently heavily debated. However, most currently available reproducibility measures depend on thresholds for the test statistics and cannot be use to evaluate overall study reproducibility. It is also crucial to elucidate the relationship between overall study reproducibility and sample size in an experimental design. In this study, we proposed a model-based reproducibility index to quantify reproducibility which could be used in large-scale high-throughput MRI-based studies including both association studies and task-induced brain activation. We performed the model-based reproducibility assessments for a few association studies and task-induced brain activation by using several recent large sMRI/fMRI databases. For large sample size association studies between brain structure/function features and some basic physiological phenotypes (i.e. Sex, BMI), we demonstrated that the model-based reproducibility of these studies is more than 0.99. For MID task activation, similar results could be observed. Furthermore, we proposed a model-based analytical tool to evaluate minimal sample size for the purpose of achieving a desirable model-based reproducibility. Additionally, we evaluated the model-based reproducibility of gray matter volume (GMV) changes for UK Biobank (UKB) vs. Parkinson Progression Marker Initiative (PPMI) and UK Biobank (UKB) vs. Human Connectome Project (HCP). We demonstrated that both sample size and study-specific experimental factors play important roles in the model-based reproducibility assessments for different experiments. In summary, a systematic assessment of reproducibility is fundamental and important in the current large-scale high-throughput MRI-based studies.

Asymmetric septal edema masking as hypertrophy in an infant with COVID-19 myocarditis.

Cardiac disease in pediatric patients due to coronavirus SARS-CoV-2 disease (COVID-19) includes myocarditis and multisystem inflammatory syndrome, both of which can present with a broad range in severity. Here we describe an infant with COVID-19 causing fulminant myocarditis with inotrope-resistant acute heart failure requiring extracorporeal membrane oxygenation. The patient demonstrated an atypical finding of localized septal thickening suggestive of hypertrophic cardiomyopathy, but the diagnosis of myocarditis was confirmed by cardiac MRI. Serial echocardiography illustrated complete resolution of septal hypertrophy and normalized cardiac function. The current report highlights the potential severity of COVID-19 associated myocarditis, the potential for recovery, and the utility of cardiac MRI in confirming the mechanism.

Demographic variables of Vestibular schwannoma's patients presented in Radio Surgical out- patient department of Cyberknife Robotic Radiosurgery, JPMC Karachi.

OBJECTIVE: To determine the age, gender and sites of vestibular schwannoma cases using contrast-enhanced magnetic resonance imaging. METHOD: The retrospective descriptive study was conducted at the Department of Cyberknife Robotic Radiosurgery, Jinnah Postgraduate Medical Centre, Karachi, and comprised data of patients with vestibular schwannomas from January 2016 to September 2018. Some of them were histologically proven and rest were radiologically proven. Cases were reviewed on contrast-enhanced magnetic resonance imaging of the brain. Statistical Package for the Social Sciences version 20 (SPSS) was applied. RESULTS: Of the 500 cases of vestibular schwannomas identified with 515 tumours, 300(60%) were males and 200(40%) were female. The overall mean age was 42.7±14.4 years (range: 17-85 years). Out of 515 tumours, the commonest site was the right cerebellopontine angle in 340(66%) cases. There were 15(3%) cases of radiologically-proven neurofibromatosis type 2. Overall, 490(98%) patients had main clinical complaint of progressive unilateral hearing loss, 5(1%) had vertigo and 5(1%) had facial palsy. CONCLUSIONS: Vestibular schwannomas were found to be more common among adults, with male preponderance and right cerebellopontine angle being the common site.

Neurovascular and cortical responses to hyperoxia: enhanced cognition and electroencephalographic activity despite reduced perfusion.

KEY POINTS: Extreme aviation is accompanied by ever-present risks of hypobaric hypoxia and decompression sickness. Neuroprotection against those hazards is conferred through fractional inspired oxygen ( FI,O2 ) concentrations of 60-100% (hyperoxia). Hyperoxia reduces global cerebral perfusion (gCBF), increases reactive oxygen species within the brain and leads to cell death within the hippocampus. However, an understanding of hyperoxia's effect on cortical activity and concomitant levels of cognitive performance is lacking. This limits our understanding of whether hyperoxia could lower the brain's threshold of tolerance to physiological stressors inherent to extreme aviation, such as high gravitational forces. This study aimed to quantify the impact of hyperoxia upon global cerebral perfusion (gCBF), cognitive performance and cortical electroencephalography (EEG). Hyperoxia evoked a rapid reduction in gCBF, yet cognitive performance and vigilance were enhanced. EEG measurements revealed enhanced alpha power, suggesting less desynchrony, within the cortical temporal regions. Collectively, this work suggests hyperoxia-induced brain hypoperfusion is accompanied by enhanced cognitive processing and cortical arousal. ABSTRACT: Extreme aviators continually inspire hyperoxic gas to mitigate risk of hypoxia and decompression injury. This neuroprotection carries a physiological cost: reduced cerebral perfusion (CBF). As reduced CBF may increase vulnerability to ever-present physiological challenges during extreme aviation, we defined the magnitude and duration of hyperoxia-induced changes in CBF, cortical electrical activity and cognition in 30 healthy males and females. Magnetic resonance imaging with pulsed arterial spin labelling provided serial measurements of global CBF (gCBF), first during exposure to 21% inspired oxygen ( FI,O2 ) followed by a 30-min exposure to 100% FI,O2 . High-density EEG facilitated characterization of cortical activity during assessment of cognitive performance, also measured during exposure to 21% and 100% FI,O2 . Acid-base physiology was measured with arterial blood gases. We found that exposure to 100% FI,O2 reduced gCBF to 63% of baseline values across all participants. Cognitive performance testing at 21% FI,O2 was accompanied by increased theta and beta power with decreased alpha power across multiple cortical areas. During cognitive testing at 100% FI,O2 , alpha activity was less desynchronized within the temporal regions than at 21% FI,O2 . The collective hyperoxia-induced changes in gCBF, cognitive performance and EEG were similar across observed partial pressures of arterial oxygen ( PaO2 ), which ranged between 276-548 mmHg, and partial pressures of arterial carbon dioxide ( PaCO2 ), which ranged between 34-50 mmHg. Sex did not influence gCBF response to 100% FI,O2 . Our findings suggest hyperoxia-induced reductions in gCBF evoke enhanced levels of cortical arousal and cognitive processing, similar to those occurring during a perceived threat.

Severe pre-eclamptic women with headache: is posterior reversible encephalopathy syndrome an associated concurrent finding?

BACKGROUND: A high incidence of posterior reversible encephalopathy syndrome (PRES) has been observed in women with eclampsia on imaging. However this association was documented mostly after convulsions occurred. This study aimed to detect the development of PRES using magnetic resonance imaging (MRI) in women with severe preeclampsia and headache, and evaluate the clinical and radiological findings in obstetric outcomes. METHODS: A prospective single-center cohort study comprising 20 pregnant women with severe pre-eclampsia related headache was conducted using Numeric Rating Scale (NRS) score of ≧4. Additionally, non-contrast brain MRI was used to detect PRES and related radiological central nervous system (CNS) abnormalities. RESULTS: Patients were enrolled at a mean gestational age of 32 weeks (range 29-38 weeks). Two women were unable to complete the scanning. Of the 18 MRI scans, 15 (83%) revealed abnormal findings. One patient developed an altered mental state and diffuse PRES, with the occipital, temporal, thalamus, and basal ganglia, the brain stem, and the cerebellum being affected. Two patients had abnormal susceptibility-weighted imaging (SWI) findings, indicating micro-hemorrhages. The majority (12 cases, 66%) of the patients had abnormal cortical hyperintensities in the occipital and temporal lobes. Only three patients had normal MRI pictures. None of the women had eclampsia occurred during the peripartum period, and only one unrelated neonatal death due to congenital anomalies. CONCLUSION: A high incidence of abnormal cortical hyperintensity changes at locations typical for PRES on MRI was noted in women with severe pre-eclampsia and headache. These early hypertensive neurological signs allowed prompt and efficient obstetrical management, to prevent the development of eclampsia and PRES.

Fraxetin inhibits interleukin-1ß-induced apoptosis, inflammation, and matrix degradation in chondrocytes and protects rat cartilage in vivo.

Osteoarthritis (OA) is a disease characterized by degeneration of the joint complex due to cartilage destruction. Fraxetin, a widely used and studied coumarin compound extracted from a traditional Chinese herb (Qin Pi), has shown anti-inflammatory and antioxidant properties, but its effects on OA have not been studied. In the present study, western blotting, immunofluorescence, and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) were used to evaluate the effects of fraxetin on IL-1ß-induced apoptotic activity, inflammatory responses, and catabolism in rat chondrocytes. The results showed that fraxetin prevented IL-1ß-induced apoptosis of chondrocytes and inhibited inflammatory mediator release by regulating the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB pathway in chondrocytes. Additionally, fraxetin suppressed the upregulation of matrix metalloproteinase 13 (MMP13) and degradation of collagen II in the extracellular matrix (ECM). Moreover, the effects of fraxetin in vivo were assessed in a monosodium iodoacetate (MIA)-induced rat model of OA using hematoxylin and eosin (H&E) and Safranin O-fast green staining and magnetic resonance imaging (MRI). The results showed that fraxetin protected the cartilage against destruction. In conclusion, fraxetin could be a potential therapeutic for OA.

Radiotherapy for the treatment of pituitary adenomas: A dosimetric comparison of three planning techniques.

AIM: Our goal was to compare conformal 3D (C3D) radiotherapy (RT), modulated intensity RT (IMRT), and volumetric modulated arc therapy (VMAT) planning techniques in treating pituitary adenomas. BACKGROUND: RT is important for managing pituitary adenomas. Treatment planning advances allow for higher radiation dosing with less risk of affecting organs at risk (OAR). MATERIALS AND METHODS: We conducted a 5-year retrospective review of patients with pituitary adenoma treated with external beam radiation therapy (C3D with flattening filter, flattening filter-free [FFF], IMRT, and VMAT). We compared dose-volume histogram data. For OARs, we recorded D2%, maximum, and mean doses. For planning target volume (PTV), we registered V95%, V107%, D95%, D98%, D50%, D2%, minimum dose, conformity index (CI), and homogeneity index (HI). RESULTS: Fifty-eight patients with pituitary adenoma were included. Target-volume coverage was acceptable for all techniques. The HI values were 0.06, IMRT; 0.07, VMAT; 0.08, C3D; and 0.09, C3D FFF (p < 0.0001). VMAT and IMRT provided the best target volume conformity (CI, 0.64 and 0.74, respectively; p < 0.0001). VMAT yielded the lowest doses to the optic pathway, lens, and cochlea. The position of the neck in extreme flexion showed that it helps in planning mainly with VMAT by allowing only one arc to be used and achieving the desired conformity, decreasing the treatment time, while allowing greater protection to the organs of risk using C3D, C3DFFF. CONCLUSIONS: Our results confirmed that EBRT in pituitary adenomas using IMRT, VMAT, C3D, C3FFF provide adequate coverage to the target. VMAT with a single arc or incomplete arc had a better compliance with desired dosimetric goals, such as target coverage and normal structures dose constraints, as well as shorter treatment time. Neck extreme flexion may have benefits in treatment planning for better preservation of organs at risk. C3D with extreme neck flexion is an appropriate treatment option when other treatment techniques are not available.

Magnetic resonance evaluation of knee osteoarthritis among the Saudi Population.

BACKGROUND AND OBJECTIVES: Osteoarthritis (OA) is the most prevalent worldwide joint degenerative disorder with high morbidities and disabilities. The current study aimed to investigate the prevalence of knee osteoarthritis (KOA) in Arar by using magnetic resonance imaging (MRI). METHODS: The prevalence of KOA was studied in Arar through MRI evaluation of randomly chosen sample from patients and their relatives attending the Prince Abdul Aziz Bin Mussad Hospital from October 2015 to November 2016. RESULTS: A total of 410 participants were enrolled in the study [328 (80%) male and 82 (20%) females]. After MRI, 163 participants [39.75% (95% CI) = 35.14 - 44.57%)] were diagnosed with KOA. The prevalence of OA was about 25.6% (95% CI = 20.8 - 31.1%) below the age of 40 years, which was found to increase by age in the enrolled volunteers. KOA prevalence was higher in females than males (75.6% and 27.7% respectively). There was a significant association between the age and genders of the participants and the prevalence of OA (p-value < 0.0001 for both variables). There was also a significant association between the age and gender of the participants and the MRI-estimated grading (p-value < 0.0001 and 0.0044 respectively). CONCLUSION: KOA is a common disease among Arar young population, especially females. Its prevalence increases by age with higher grades of severity affecting the elderly.

Unresectable recurrence malignant sacrococcygeal teratoma in children treated with chemoradiotherapy: Case report and literature review.

Sacrococcygeal teratoma is the most common germ cell neoplasia that consists of tissues derived from primitive germ layers. Approximately 10-20% of patients are malignant. Because of the high rate of recurrence, treatment strategies for malignant sacrococcygeal teratomas are limited. Hence, we report a case of malignant sacrococcygeal teratoma treated with concurrent chemoradiotherapy plus adjuvant chemotherapy and review the literature. This case report indicates that chemoradiation plus adjuvant chemotherapy may be a treatment option for malignant SCT which is not technically resectable or with residual lesion after surgery.

The value of subtraction MRI in detection of amyloid-related imaging abnormalities with oedema or effusion in Alzheimer's patients: An interobserver study.

BACKGROUND: Immunotherapeutic treatments targeting amyloid-ß plaques in Alzheimer's disease (AD) are associated with the presence of amyloid-related imaging abnormalities with oedema or effusion (ARIA-E), whose detection and classification is crucial to evaluate subjects enrolled in clinical trials. PURPOSE: To investigate the applicability of subtraction MRI in the ARIA-E detection using an established ARIA-E-rating scale. METHODS: We included 75 AD patients receiving bapineuzumab treatment, including 29 ARIA-E cases. Five neuroradiologists rated their brain MRI-scans with and without subtraction images. The accuracy of evaluating the presence of ARIA-E, intraclass correlation coefficient (ICC) and specific agreement was calculated. RESULTS: Subtraction resulted in higher sensitivity (0.966) and lower specificity (0.970) than native images (0.959, 0.991, respectively). Individual rater detection was excellent. ICC scores ranged from excellent to good, except for gyral swelling (moderate). Excellent negative and good positive specific agreement among all ARIA-E imaging features was reported in both groups. Combining sulcal hyperintensity and gyral swelling significantly increased positive agreement for subtraction images. CONCLUSION: Subtraction MRI has potential as a visual aid increasing the sensitivity of ARIA-E assessment. However, in order to improve its usefulness isotropic acquisition and enhanced training are required. The ARIA-E rating scale may benefit from combining sulcal hyperintensity and swelling. KEY POINTS: • Subtraction technique can improve detection amyloid-related imaging-abnormalities with edema/effusion in Alzheimer's patients. • The value of ARIA-E detection, classification and monitoring using subtraction was assessed. • Validation of an established ARIA-E rating scale, recommendations for improvement are reported. • Complementary statistical methods were employed to measure accuracy, inter-rater-reliability and specific agreement.

Contrast-enhanced spectral mammography in neoadjuvant chemotherapy monitoring: a comparison with breast magnetic resonance imaging.

BACKGROUND: Neoadjuvant-chemotherapy (NAC) is considered the standard treatment for locally advanced breast carcinomas. Accurate assessment of disease response is fundamental to increase the chances of successful breast-conserving surgery and to avoid local recurrence. The purpose of this study was to compare contrast-enhanced spectral mammography (CESM) and contrast-enhanced-MRI (MRI) in the evaluation of tumor response to NAC. METHODS: This prospective study was approved by the institutional review board and written informed consent was obtained. Fifty-four consenting women with breast cancer and indication of NAC were consecutively enrolled between October 2012 and December 2014. Patients underwent both CESM and MRI before, during and after NAC. MRI was performed first, followed by CESM within 3 days. Response to therapy was evaluated for each patient, comparing the size of the residual lesion measured on CESM and MRI performed after NAC to the pathological response on surgical specimens (gold standard), independently of and blinded to the results of the other test. The agreement between measurements was evaluated using Lin's coefficient. The agreement between measurements using CESM and MRI was tested at each step of the study, before, during and after NAC. And last of all, the variation in the largest dimension of the tumor on CESM and MRI was assessed according to the parameters set in RECIST 1.1 criteria, focusing on pathological complete response (pCR). RESULTS: A total of 46 patients (85%) completed the study. CESM predicted pCR better than MRI (Lin's coefficient 0.81 and 0.59, respectively). Both methods tend to underestimate the real extent of residual tumor (mean 4.1mm in CESM, 7.5mm in MRI). The agreement between measurements using CESM and MRI was 0.96, 0.94 and 0.76 before, during and after NAC respectively. The distinction between responders and non-responders with CESM and MRI was identical for 45/46 patients. In the assessment of CR, sensitivity and specificity were 100% and 84%, respectively, for CESM, and 87% and 60% for MRI. CONCLUSION: CESM and MRI lesion size measurements were highly correlated. CESM seems at least as reliable as MRI in assessing the response to NAC, and may be an alternative if MRI is contraindicated or its availability is limited.

Use of Pig as a Model for Mesenchymal Stem Cell Therapies for Bone Regeneration.

Bone is a plastic tissue with a large healing capability. However, extensive bone loss due to disease or trauma requires extreme therapy such as bone grafting or tissue-engineering applications. Presently, bone grafting is the gold standard for bone repair, but presents serious limitations including donor site morbidity, rejection, and limited tissue regeneration. The use of stem cells appears to be a means to overcome such limitations. Bone marrow mesenchymal stem cells (BMSC) have been the choice thus far for stem cell therapy for bone regeneration. However, adipose-derived stem cells (ASC) have similar immunophenotype, morphology, multilineage potential, and transcriptome compared to BMSC, and both types have demonstrated extensive osteogenic capacity both in vitro and in vivo in several species. The use of scaffolds in combination with stem cells and growth factors provides a valuable tool for guided bone regeneration, especially for complex anatomic defects. Before translation to human medicine, regenerative strategies must be developed in animal models to improve effectiveness and efficiency. The pig presents as a useful model due to similar macro- and microanatomy and favorable logistics of use. This review examines data that provides strong support for the clinical translation of the pig model for bone regeneration.

Evaluation of response after SBRT for liver tumors.

Stereotactic body radiotherapy (SBRT) has developed over the last few years for the treatment of primary and metastatic hepatic tumors. The tumoral and adjacent peritumoral modifications caused by this radiosurgery limit the evaluation of response by anatomic imaging and dimensional criteria alone, such as with RECIST. This suggests that it is of interest to also take into account the residual enhancement and hyper metabolism of these hepatic targets. We have reviewed the English language literature regarding the response of hepatic lesions treated by SBRT, and found that only seven articles were specifically concerned with this problem. The response of the hepatocellular carcinoma after SBRT has been studied specifically with multiphase enhanced CT-scan. Criteria set by the European Association of Study of the Liver better estimate response at each time point of follow up than RECIST does. Non-enhancement, reflecting tumor necrosis, is additionally an early indicator of response with extended response in time and a best non-enhancement percentage is observed at 12 months. The response after treatment by SBRT of cholangiocarcinoma has not yet generated a specific report. Use of RECIST criteria is also inadequate in the evaluation of response after SBRT for hepatic metastases. Response of liver metastases to SBRT is better assessed with a combination of size and enhancement pattern. The occurrence of a lobulated enhancement during follow up is efficient to predict local progression in a specific, reproducible, and sensitive way. Patients with FDG-avid hepatic metastases are also better evaluated with PET-CT and functional criteria than routine imaging and metric evaluation alone.

Imaging changes after breast reconstruction with fat grafting - Retrospective study of 90 breast cancer.

OBJECTIVE: To evaluate the breast imaging changes after fat grafting and its impact on cancer follow up. METHODS: This is a retrospective observational study conducted on patients who underwent fat grafting for breast reconstruction. We reviewed mammographic and ultrasound images of patients. Fisher's exact test was used to analyze results. The level of significance was set at P < 0.05. RESULTS: A total of ninety patients with breast cancer had fat grafting. Fifty eight patients for defects following post mastectomy reconstruction and 32 for wide local excision defects. The mean follow up was 37.4 months. Benign lumps were identified in 23/90 cases (25 percent). Mammograms were reported as BI-RADS I in 21/32 cases (72 percent) and BI-RADS II in 8/32 cases (28 percent). BI-RADs III score was reported in two patients on further follow up imaging, both were re-classified as BI-RADS II after biopsy. A total of eight patients (8.9 percent) required biopsy. No local recurrences or new cancers were observed in any patients. CONCLUSION: Our study suggests radiological changes after fat grafting are almost always benign with no adverse outcome on cancer follow up.

Outcome of radiotherapy for pituitary adenomas.

AIM: The aim of this study was to analyze the outcome and toxicities and its correlation to patient related and treatment related factors. BACKGROUND: Pituitary adenomas are treated by radiation therapy (RT) as one of the modalities along with surgery and medical therapy. RT to pituitary adenomas is a challenge due to adjacent dose limiting structures such as optic apparatus and hypothalamus. MATERIALS AND METHODS: Between January 2004 and December 2010, 94 patients treated for pituitary adenoma with RT who had hospital records of a minimum follow-up of 1 year were included in the analysis. Tests of correlation were done with regards to treatment factors. RESULTS: Male preponderance was noted in our patient population. Nonfunctioning and functioning tumors were equal in number in this series. Hypopituitarism was associated in 58.5% of patients prior to RT. Radiological tumor progression was seen in one patient (1/94) who had a nonfunctioning tumor. Among functioning tumors, biochemical remission was seen in 93.6% of patients at a median follow-up of 6 years. CONCLUSIONS: Visual complication was seen in 5.3% of patients and worsening or new onset hypopituitarism was seen in 6.4%. Conventional 3-field technique was associated with significantly more visual complication compared to Stereotactic Radiation Therapy (SRT) technique. Doses ≤50.4 Gy showed a trend of reduced rate of visual and endocrine complications with no compromise in efficacy.

Susceptibility-weighted imaging and quantitative susceptibility mapping in the brain.

Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique that enhances image contrast by using the susceptibility differences between tissues. It is created by combining both magnitude and phase in the gradient echo data. SWI is sensitive to both paramagnetic and diamagnetic substances which generate different phase shift in MRI data. SWI images can be displayed as a minimum intensity projection that provides high resolution delineation of the cerebral venous architecture, a feature that is not available in other MRI techniques. As such, SWI has been widely applied to diagnose various venous abnormalities. SWI is especially sensitive to deoxygenated blood and intracranial mineral deposition and, for that reason, has been applied to image various pathologies including intracranial hemorrhage, traumatic brain injury, stroke, neoplasm, and multiple sclerosis. SWI, however, does not provide quantitative measures of magnetic susceptibility. This limitation is currently being addressed with the development of quantitative susceptibility mapping (QSM) and susceptibility tensor imaging (STI). While QSM treats susceptibility as isotropic, STI treats susceptibility as generally anisotropic characterized by a tensor quantity. This article reviews the basic principles of SWI, its clinical and research applications, the mechanisms governing brain susceptibility properties, and its practical implementation, with a focus on brain imaging.

Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas.

Introduction of ligands into 100 nm scaled hollow capsules has great potential for diagnostic and therapeutic applications in drug delivery systems. Polyethylene glycol-conjugated (PEGylated) polyion complex vesicles (PICsomes) are promising hollow nano-capsules that can survive for long periods in the blood circulation and can be used to deliver water-soluble macromolecules to target tissues. In this study, cyclic RGD (cRGD) peptide, which is specifically recognized by αVß3 and αvß5 integrins that are expressed at high levels in the neovascular system, was conjugated onto the distal end of PEG strands on PICsomes for active neovascular targeting. Density-tunable cRGD-conjugation was achieved using PICsomes with definite fraction of end-functionalized PEG, to substitute 20, 40, and 100% of PEG distal end of the PICsomes to cRGD moieties. Compared with control-PICsomes without cRGD, cRGD-PICsomes exhibited increased uptake into human umbilical vein endothelial cells. Intravital confocal laser scanning microscopy revealed that the 40%-cRGD-PICsomes accumulated mainly in the tumor neovasculature and remained in the perivascular region even after 24 h. Furthermore, we prepared superparamagnetic iron oxide (SPIO)-loaded cRGD-PICsomes for magnetic resonance imaging (MRI) and successfully visualized the neovasculature in an orthotopic glioblastoma model, which suggests that SPIO-loaded cRGD-PICsomes might be useful as a MRI contrast reagent for imaging of the tumor microenvironment, including neovascular regions that overexpress αVß3 integrins.

Fractionated stereotactic radiotherapy plus bevacizumab after response to bevacizumab plus irinotecan as a rescue treatment for high-grade gliomas.

AIM: To evaluate the possibility of implementing a new scheme of rescue treatment after relapse or progression of high-grade glioma (HGG) treated at the first-line with bevacizumab and irinotecan (BVZ+CPT11), evaluating the response and toxicity of associating BVZ and fractionated stereotactic radiotherapy (BVZ+FSRT). MATERIALS AND METHODS: We retrospectively analysed data from 59 patients with relapse of HGG. Nine patients with HGG relapse after treatment using the Stupp protocol that were treated with BVZ+CPT11 for progression between July 2007 and August 2012, after which the response was assessed according to the Revised Assessment in Neuro-Oncology (RANO) criteria. BVZ was administered at a dose of 10 mg/kg and FSRT up to a prescribed dose of 30 Gy, 500 cGy per fraction, three days a week. The median follow-up was 38 months. RESULTS: The treatment was well-tolerated by all patients. The response after nuclear magnetic resonance imaging (MRI) at 3-6 months was progression in two patients, stable disease in four, and three patients had a partial response. The median overall survival (OS) from diagnosis until death or the last control was 36.8 months. The median progression-free survival (PFS) was 10.8 months. The results from tumour sub-group analysis indicated that the PFS was not statistically significant although it seemed that it was higher in grade-III. The OS was higher in grade-III gliomas. CONCLUSIONS: The combination of BVZ+FSRT as a second-line HGG relapse rescue treatment is well-tolerated and seems to offer promising results. We believe that multi-centre prospective studies are needed to determine the long-term efficacy and toxicity of this therapeutic approach.