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Objective: This study investigated the safety and efficacy of sclerotherapy with intralesional bleomycin injection (IBI) for retrobulbar orbital low-flow vascular lesions under multi-slice computed tomography (CT) guidance., Methods: Between January 2010 and September 2021, consecutive patients with retrobulbar orbital low-flow vascular lesions who underwent CT-guided IBI at a tertiary centre in Taiwan were enrolled. Their medical records and imaging data were retrospectively collected., Results: This study enrolled 13 patients (7 male and 6 female patients; age range: 1-57 years; mean age: 25.9 years) with lymphatic malformation (LM, n = 4), venolymphatic malformation (n = 1), and venous malformation (VM, n = 8). The overall radiological response rate was 76.9% (10 of 13); the radiological response rate was 75.0% in the VM group (6 of 8) and 75.0% in the LM group (3 of 4). Moreover, 3 patients (23.1%) had minor complications and 1 (7.7%) had a major complication. The mean clinical and radiological follow-up was 8.3 months and no recurrence or progression was reported., Conclusion: CT-guided IBI is an effective and relatively safe minimally invasive treatment for retrobulbar orbital low-flow vascular lesions, with an overall radiological response rate of 76.9% in a mean of 1.5 sessions and a low complication rate., Advances in Knowledge: CT-guided sclerotherapy with IBI is a relatively safe, effective, and feasible alternative treatment option for retrobulbar orbital low-flow vascular lesions., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Rotational angiography acquires radiographs at multiple projection angles to demonstrate superimposed vasculature. However, this comes at the expense of the inherent risk of increased ionizing radiation. In this paper, building upon a successful deep learning model, we developed a novel technique to super-resolve the radiography at different projection angles to reduce the actual projections needed for a diagnosable radiographic procedure., Methods: Ten models were trained for different levels of angular super-resolution (ASR), denoted as ASRN, where for every N+2 frames, the first and the last frames were submitted as inputs to super-resolve the intermediate N frames., Results: The results show that large arterial structures were well preserved in all ASR levels. Small arteries were adequately visualized in lower ASR levels but progressively blurred out in higher ASR levels. Noninferiority of image quality was demonstrated in ASR1-4 (99.75% confidence intervals: -0.16-0.03, -0.19-0.04, -0.17-0.01, -0.15-0.05 respectively)., Conclusions: ASR technique is capable of super-resolving rotational angiographic frames at intermediate projection angles., Competing Interests: Conflicts of interest The authors have filed U.S. (17210604) and Taiwan (109114132) patent applications related to this work., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

A reliable prognostic stratification of patients with locally advanced hypopharyngeal cancer who had been treated with concurrent chemoradiotherapy (CCRT) is crucial for informing tailored management strategies. The purpose of this retrospective study was to develop robust and objective magnetic resonance imaging (MRI) radiomics-based models for predicting overall survival (OS) and progression-free survival (PFS) in this patient population. The study participants included 198 patients (median age: 52.25 years (interquartile range = 46.88-59.53 years); 95.96% men) who were randomly divided into a training cohort ( n = 132) and a testing cohort ( n = 66). Radiomic parameters were extracted from post-contrast T1-weighted MR images. Radiomic features for model construction were selected from the training cohort using least absolute shrinkage and selection operator-Cox regression models. Prognostic performances were assessed by calculating the integrated area under the receiver operating characteristic curve (iAUC). The ability of radiomic models to predict OS (iAUC = 0.580, 95% confidence interval (CI): 0.558-0.591) and PFS (iAUC = 0.625, 95% CI = 0.600-0.633) was validated in the testing cohort. The combination of radiomic signatures with traditional clinical parameters outperformed clinical variables alone in the prediction of survival outcomes (observed iAUC increments = 0.279 [95% CI = 0.225-0.334] and 0.293 [95% CI = 0.232-0.351] for OS and PFS, respectively). In summary, MRI radiomics has value for predicting survival outcomes in patients with hypopharyngeal cancer treated with CCRT, especially when combined with clinical prognostic variables.

Background and Objectives: The glymphatic system, which is robustly enabled during some stages of sleep, is a fluid-transport pathway that clears cerebral waste products. Most contemporary knowledge regarding the glymphatic system is inferred from rodent experiments and human research is limited. Our objective is to explore the associations between human glymphatic function, sleep, neuropsychological performance, and cerebral gray matter volumes., Methods: This cross-sectional study included individuals 60 years or older who had participated in the Integrating Systemic Data of Geriatric Medicine to Explore the Solution for Health Aging study between September 2019 and October 2020. Community-dwelling older adults were enrolled at 2 different sites. Participants with dementia, major depressive disorders, and other major organ system abnormalities were excluded. Sleep profile was accessed using questionnaires and polysomnography. Administered neuropsychological test batteries included Everyday Cognition (ECog) and the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB). Gray matter volumes were estimated based on MRI. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index was used as the MRI marker of glymphatic function., Results: A total of 84 participants (mean [SD] age 73.3 [7.1] years, 47 [56.0%] women) were analyzed. Multivariate linear regression model determined that age (unstandardized β, -0.0025 [SE 0.0001]; p = 0.02), N2 sleep duration (unstandardized β, 0.0002 [SE 0.0001]; p = 0.04), and the apnea-hypopnea index (unstandardized β, -0.0011 [SE 0.0005]; p = 0.03) were independently associated with DTI-ALPS. Higher DTI-ALPS was associated with better ECog language scores (unstandardized β, -0.59 [SE 0.28]; p = 0.04) and better CERAD-NB word list learning delayed recall subtest scores (unstandardized β, 6.17 [SE 2.31]; p = 0.009) after covarying for age and education. Higher DTI-ALPS was also associated with higher gray matter volume (unstandardized β, 107.00 [SE 43.65]; p = 0.02) after controlling for age, sex, and total intracranial volume., Discussion: Significant associations were identified between glymphatic function and sleep, stressing the importance of sleep for brain health. This study also revealed associations between DTI-ALPS, neuropsychological performance, and cerebral gray matter volumes, suggesting the potential of DTI-ALPS as a biomarker for cognitive disorders., (© 2021 American Academy of Neurology.)

Introduction: Postoperative cerebellar mutism syndrome (pCMS) consists of three types of symptoms (motoric, linguistic, and neurobehavioral) in patients with posterior fossa pathologies. The evolutional mechanism of this high cognitive syndromic complex from cerebellar origin remains unconfirmed. Previous studies analyzing CMS patients mostly focused on the association between structural abnormalities that occur during CMS, of which proximal efferent cerebellar pathway (pECP) injury appears to be the most common pathogenesis. However, structural imaging may not be sensitive enough to determine the dynamic course of CMS, since the symptomatology is primarily an output of cerebral operation., Method: We took a network approach in a child during her course of development and recovery of the pCMS. On the other hand, a network neuroscience approach using a mathematical model to extract information from functional imaging to generate interregional connectivity provides abundant evidence that the cerebellum is influential in modulating cerebral functions., Result: This study applied a network approach to children with pCMS. An individual cerebrocerebellar functional network analysis using graph theory was then performed to determine the network dynamics during CMS. Cross-validation of clinical neurophysiology and functional neuroscience suggested the critical role of the pECP within CMS from the network analysis., Conclusion: The employed approach was therefore useful in determining the complex clinical symptoms using individual functional network analysis, which bridges the gap between structural neuroimaging and clinical neurophysiology., (© The Author(s) 2022. Published by Oxford University Press.)

Cortical reorganization occurs immediately after peripheral nerve injury, and early sensorimotor training is suggested during nerve regeneration. The effect of mirror therapy and classical sensory relearning on cortical activation immediately after peripheral nerve repair of the forearm is unknown. Six participants were randomly assigned to the mirror-therapy group or the sensory-relearning group. Sensorimotor training was conducted in a mirror box for 12 weeks. The mirror-therapy group used mirror reflection of the unaffected hand in order to train the affected hand, and the sensory-relearning group trained without mirror reflection. Semmes-Weinstein Monofilaments (SWM) test, static 2-point discrimination test (S-2PD), grip strength, and the Disabilities of the Arm, Shoulder and Hand (DASH) scores were measured at baseline, the end of the intervention (T1), and 3 months after the intervention (T2). Finger and manual dexterity were measured at T1 and T2, and a functional MRI (fMRI) was conducted at T1. All participants showed improvement in the SWM, S-2PD tests, upper extremity function, and grip strength after the intervention at T1, except for the participant who injured both the median and ulnar nerves in the sensory-relearning group. In addition, the mirror-therapy group had better outcomes in finger dexterity and manual dexterity, and fMRIs showed greater activation in the multimodal association cortices and ipsilateral brain areas during motor tasks. This study provides evidence-based results confirming the benefits of early sensorimotor relearning for cortical activation in peripheral nerve injury of the forearm and different neuroplasticity patterns between mirror therapy and classical sensor relearning., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Rodent experiments have provided some insight into the changes of glymphatic function in ischemic stroke. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method offers an opportunity for the noninvasive investigation of the glymphatic system in patients with ischemic stroke. We aimed to investigate the changes of glymphatic function in ischemic stroke and the factors associated with the changes. Materials and Methods: A total of 50 patients (mean age 56.7 years; 30 men) and 44 normal subjects (mean age 53.3 years; 23 men) who had preoperative diffusion-tensor imaging for calculation of the analysis along the perivascular space (ALPS) index were retrospectively included. Information collected from each patient included sex, age, time since stroke onset, infarct location, hemorrhagic change, infarct volume, infarct apparent diffusion coefficient (ADC), infarct fractional anisotropy (FA), and ALPS index of both hemispheres. Interhemispheric differences in ALPS index (infarct side vs. contralateral normal side) were assessed with a paired t -test in all patients. ALPS index was normalized by calculating ALPS ratios (right-to-left and left-to-right) for comparisons between patients and normal subjects. Comparisons of ALPS ratios between patients and normal subjects were performed using analysis of covariance with adjustments for age and sex. Linear regression analyses were performed to identify factors associated with the ALPS index. Results: In patients, the mean ALPS index ipsilateral to infarct was 1.162 ± 0.126, significantly lower ( P < 0.001) than that of the contralateral side (1.335 ± 0.160). The right-to-left ALPS index ratio of patients with right cerebral infarct was 0.84 ± 0.08, significantly lower ( P < 0.001) than that of normal subjects (0.95 ± 0.07). The left-to-right ALPS ratio of patients with left cerebral infarct was 0.92 ± 0.09, significantly ( P < 0.001) lower than that of normal subjects (1.05 ± 0.08). On multiple linear regression analysis, time since stroke onset (β = 0.794, P < 0.001) was the only factor associated with the ALPS index. Conclusion: The ALPS index showed lower values in ischemic stroke suggesting impaired glymphatic function. Following initial impairment, the ALPS index increased with the time since stroke onset, which is suggestive of glymphatic function recovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Toh and Siow.)

Objectives: The proliferation of microvessels with increased permeability is thought to be the cause of peritumoral brain edema (PTBE) in metastases. The contribution of the glymphatic system to the formation of PTBE in brain metastases remains unexplored. We aimed to investigate if the PTBE volume of brain metastases is related to glymphatic dysfunction., Materials and Methods: A total of 56 patients with brain metastases who had preoperative dynamic susceptibility contrast-enhanced perfusion-weighted imaging for calculation of tumor cerebral blood volume (CBV) and diffusion tensor imaging for calculations of tumor apparent diffusion coefficient (ADC), tumor fractional anisotropy (FA), and analysis along perivascular space (ALPS) index were analyzed. The volumes of PTBE, whole tumor, enhancing tumor, and necrotic and hemorrhagic portions were manually measured. Additional information collected for each patient included age, sex, primary cancer, metastasis location and number, and the presence of concurrent infratentorial tumors. Linear regression analyses were performed to identify factors associated with PTBE volume., Results: Among 56 patients, 45 had solitary metastasis, 24 had right cerebral metastasis, 21 had left cerebral metastasis, 11 had bilateral cerebral metastases, and 11 had concurrent infratentorial metastases. On univariable linear regression analysis, PTBE volume correlated with whole tumor volume ( β = -0.348, P = 0.009), hemorrhagic portion volume ( β = -0.327, P = 0.014), tumor ADC ( β = 0.530, P <.001), and ALPS index ( β = -0.750, P <.001). The associations of PTBE volume with age, sex, tumor location, number of tumors, concurrent infratentorial tumor, enhancing tumor volume, necrotic portion volume, tumor FA, and tumor CBV were not significant. On multivariable linear regression analysis, tumor ADC ( β = 0.303; P = 0.004) and ALPS index ( β = -0.624; P < 0.001) were the two independent factors associated with PTBE volume., Conclusion: Metastases with higher tumor ADC and lower ALPS index were associated with larger peritumoral brain edema volumes. The higher tumor ADC may be related to increased periarterial water influx into the tumor interstitium, while the lower ALPS index may indicate insufficient fluid clearance. The changes in both tumor ADC and ALPS index may imply glymphatic dysfunction, which is, at least, partially responsible for peritumoral brain edema formation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Toh, Siow and Castillo.)

Using only increasing contrast enhancement as a marker of malignant transformation (MT) in gliomas has low specificity and may affect interpretation of clinical outcomes. Therefore we developed a mathematical model to predict MT of low-grade gliomas (LGGs) by considering areas of reduced apparent diffusion coefficient (ADC) with increased contrast enhancement. Patients with contrast-enhancing LGGs who had contemporaneous ADC and histopathology were retrospectively analyzed. Multiple clinical factors and imaging factors (contrast-enhancement size, whole-tumor size, and ADC) were assessed for association with MT. Patients were split into training and validation groups for the development of a predictive model using logistic regression which was assessed with receiver operating characteristic analysis. Among 132 patients, (median age 46.5 years), 106 patients (64 MT) were assigned to the training group and 26 (20 MT) to the validation group. The predictive model comprised age ( P = 0.110), radiotherapy ( P = 0.168), contrast-enhancement size ( P = 0.015), and ADC ( P < 0.001). The predictive model (area-under-the-curve [AUC] 0.87) outperformed ADC (AUC 0.85) and contrast-enhancement size (AUC 0.67). The model had an accuracy of 84% for the training group and 85% respectively for the validation group. Our model incorporating ADC and contrast-enhancement size predicted MT in contrast-enhancing LGGs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wong, Siow, Wei, Chen, Toh and Castillo.)

Objectives: Rodent experiments have provided some insights into the changes of glymphatic function associated with glioma growth. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method offers an opportunity for the noninvasive investigation of the glymphatic system in patients with glioma. We aimed to investigate the factors associated with glymphatic function changes in patients with glioma., Materials and Methods: A total of 201 glioma patients (mean age = 47.4 years, 116 men; 86 grade II, 52 grade III, and 63 grade IV) who had preoperative diffusion tensor imaging for calculation of the ALPS index were retrospectively included. Information collected from each patient included sex, age, tumor grade, isocitrate dehydrogenase 1 ( IDH1 ) mutation status, peritumoral brain edema volume, tumor volume, and ALPS index. Group differences in the ALPS index according to sex, tumor grade, and IDH1 mutation status were assessed using analysis of covariance with age adjustment. Linear regression analyses were performed to identify the factors associated with the ALPS index., Results: Group comparisons revealed that the ALPS index of grade II/III gliomas was significantly higher than that of grade IV gliomas ( p < 0.001). The ALPS index of IDH1 mutant gliomas was significantly higher than that of IDH1 wild-type gliomas ( p < 0.001). On multivariable linear regression analysis, IDH1 mutation ( β = 0.308, p < 0.001) and peritumoral brain edema volume ( β = -0.353, p < 0.001) were the two independent factors associated with the ALPS index., Conclusion: IDH1 wild-type gliomas and gliomas with larger peritumoral brain edema volumes were associated with a lower ALPS index, which may reflect impaired glymphatic function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Toh and Siow.)

Background: Obtaining pus for microbial cultures is one of the surgical aims in patients with brain abscess. Predictors of microbial yields are necessary as they help in treatment planning., Purpose: To investigate the relationship between microbial culture yields of brain abscesses and their apparent diffusion coefficient (ADC) values and clinical characteristics., Study Type: Retrospective., Subjects: Eighty-four patients diagnosed with brain abscess by surgery and histopathology (59 with positive abscess cultures)., Field Strength/sequence: Diffusion-weighted, T2-weigthed, and contrast-enhanced T1-weighted imaging at 1.5 T and 3 T., Assessment: Contrast-enhanced T1-weighted images were co-registered to ADC maps. Three neuroradiologists determined abscess imaging characteristics (distribution, location, and ventricular rupture), and two measured abscess volumes and ADC values. Clinical characteristics collected included sex, age, fever, underlying diseases, infection sources, white blood cell count, percentage of segmented neutrophils, C-reactive protein level, regimen and duration of empirical antibiotics, and types of surgery., Statistical Tests: Interobserver differences were assessed with Fleiss kappa and intraclass correlation coefficients. The differences in clinical and imaging factors between the positive and negative culture groups were compared with Chi-square analysis or Student's t test. All factors were subjected to multivariable logistic regression analysis to assess their associations with microbial culture yields, and factors with statistical significance were evaluated with receiver operating characteristic curve analysis to assess their diagnostic performance in discriminating the two groups., Results: Mean ADC (×10 -6  mm 2 /s) of culture-negative abscesses (841 ± 173) was significantly higher (P < 0.05) than that of culture-positive abscesses (536 ± 90). On multivariable analysis, mean ADC was the only significant factor (P < 0.05) related to culture yields. With 660 as the cutoff value, the sensitivity, specificity, and accuracy of ADC for discriminating culture yields were 93.2%, 88.0%, and 91.7%, respectively., Data Conclusion: ADC could be used to discriminate between culture-positive and culture-negative abscesses., Evidence Level: 4 TECHNICAL EFFICACY: Stage 2., (© 2021 International Society for Magnetic Resonance in Medicine.)

The pathogenesis of peritumoral brain edema (PTBE) in meningiomas remains unclear. The glymphatic system is recently recognized as a pathway for waste clearance and maintaining fluid balance in the brain parenchymal interstitium. We aimed to investigate if the PTBE volume of meningiomas correlates with their glymphatic function. A total of 80 meningioma patients (mean age, 58.8 years; 37 men) and 44 normal subjects (mean age 53.3 years; 23 men) who had preoperative diffusion-tensor imaging for calculation of the analysis along the perivascular space (ALPS) index were retrospectively included. Information collected from each patient included sex, age, tumor grade, Ki-67 index, tumor location, tumor volume, PTBE volume and ALPS index. Comparisons of ALPS index among meningiomas without PTBE, meningiomas with PTBE, and normal subjects were performed using analysis of covariance with Bonferroni correction and adjustments for age and sex. Pearson correlation coefficient and multivariable linear regression analyses were performed to identify factors associated with PTBE volume. Group comparisons revealed that the ALPS index was significantly higher ( P < 0.05) in meningiomas without PTBE vs. meningiomas with PTBE and normal subjects. On the other hand, ALPS index was not different between meningiomas with PTBE and normal subjects. On Pearson correlation and multivariable linear regression analyses, the ALPS index was the only factor significantly ( P < 0.05) associated with PTBE volume. In conclusion, PTBE volume inversely correlated with ALPS index in meningiomas. PTBE formation in meningiomas may be related to glymphatic dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Toh, Siow and Castillo.)

Precise risk stratification in lymphadenectomy is important for patients with endometrial cancer (EC), to balance the therapeutic benefit against the operation-related morbidity and mortality. We aimed to investigate added values of computer-aided segmentation and machine learning based on clinical parameters and diffusion-weighted imaging radiomics for predicting lymph node (LN) metastasis in EC. This prospective observational study included 236 women with EC (mean age ± standard deviation, 51.2 ± 11.6 years) who underwent magnetic resonance (MR) imaging before surgery during July 2010-July 2018, randomly split into training ( n = 165) and test sets ( n = 71). A decision-tree model was constructed based on mean apparent diffusion coefficient (ADC) value of the tumor (cutoff, 1.1 × 10 -3 mm 2 /s), skewness of the relative ADC value (cutoff, 1.2), short-axis diameter of LN (cutoff, 1.7 mm) and skewness ADC value of the LN (cutoff, 7.2 × 10 -2 ), as well as tumor grade (1 vs. 2 and 3), and clinical tumor size (cutoff, 20 mm). The sensitivity and specificity of the model were 94% and 80% for the training set and 86%, 78% for the independent testing set, respectively. The areas under the receiver operating characteristics curve (AUCs) of the decision-tree was 0.85-significantly higher than the mean ADC model (AUC = 0.54) and LN short-axis diameter criteria (AUC = 0.62) (both p < 0.0001). We concluded that a combination of clinical and MR radiomics generates a prediction model for LN metastasis in EC, with diagnostic performance surpassing the conventional ADC and size criteria.

Background: Persisting embryonal infundibular recess (PEIR) is a rare anomaly of the third ventricular floor, with only 10 cases having been reported to date. Accurate imaging diagnosis of this entity is essential to avoid unnecessary surgery and its associated morbidity. The following case is presented to emphasize its recognition in the differential diagnosis of pituitary cystic lesions., Case Description: A 38-year-old woman was referred for evaluation of a pituitary cystic mass. Magnetic resonance imaging (MRI) revealed a 10.2-mm cystic mass in an enlarged sella turcica. Three-dimensional high-resolution MRI using constructive interference in steady-state sequence clearly delineated a communicating tract between the third ventricle and the sellar cyst through pituitary stalk. A final diagnosis of PEIR was made. The patient was managed successfully with conservative treatment, and the lesion was in a stationary condition over a 5-year follow-up period., Conclusions: This is the first case report demonstrating imaging features of PEIR in 3-dimensional high-resolution MRI. Although PEIR is a rare anomaly, imaging diagnosis of this entity is important because confusion with other pituitary cystic lesions and the attempt of surgical removal may lead to serious complications., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The purpose of the study is to develop a targeted nanoparticle platform for T cell labeling and tracking in vivo., Procedures: Through carboxylation of the polyethylene glycol (PEG) surface of SPION, carboxylated-PEG-SPION (IOPC) was generated as a precursor for further conjugation with the targeting probe. The IOPC could readily cross-link with a variety of amide-containing molecules by exploiting the reaction between 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide and N-hydroxysuccinimide. The subsequent conjugation of monoclonal anti-CD3 antibody with IOPC made it possible to construct a magnetic resonance imaging (MRI) contrast agente (CA) that targets T cells, named IOPC-CD3., Results: IOPC-CD3 was found to have high transverse relaxivity, good targeting selectivity, and good safety profile in vitro. The utility of this newly synthesized CA was explored in an in vivo rodent collagen-induced arthritis (CIA) model of rheumatoid arthritis. Serial MRI experiments revealed a selective decrease in the signal-to-noise ratio of the femoral growth plates of CIA rats infused with IOPC-CD3, with this finding being consistent with immunohistochemical results showing the accumulation of T cells and iron oxide nanoparticles in the corresponding region., Conclusions: Together with the abovementioned desirable features, these results indicate that IOPC-CD3 offers a promising prospect for a wide range of cellular and molecular MRI applications.

Objective: Although anterior cruciate ligament (ACL) injury is a well-recognized risk factor for developing knee post-traumatic osteoarthritis (PTOA), the process in the patellofemoral (PF) joint after ACL injury is still under-researched. Our aim was to investigate the perfusion changes in PF subchondral bone marrow in the rat ACL transection (ACLX) model of PTOA using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)., Design: Eighteen male Sprague Dawley rats were randomly separated into three groups (n = 6 each group): a normal control group and groups receiving ACLX and sham-surgery, respectively, in the right knee. Perfusion parameters in the patellar and femoral subchondral bone marrows of all rats were measured on DCE-MRI at 0, 4, 8, and 16 weeks after respective treatment. After the last MRI at week 16, the rats were sacrificed and their right knees were harvested for histologic examination. In addition, to observe the long-term histologic change in PF joints, 9 additional rats (n = 3 in each group) were included and sacrificed at week 32 for histologic examination., Results: In the ACLX group vs the sham and control groups, the perfusion parameters were significantly changed in both patellar and femoral subchondral bone marrows at week 16. Histologic examination revealed cartilage defects in ACLX rats at 32 weeks after surgery., Conclusions: These data point to a possible functional relationship between subchondral bone marrow perfusion abnormalities and cartilage breakdown in PTOA. Moreover, the perfusion parameters derived from DCE-MRI can potentially serve as biomarkers of early OA., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

3,4-Methylenedioxymethamphetamine (MDMA), also known as "Ecstasy", is a common recreational drug of abuse. Several previous studies have attributed the central serotonergic neurotoxicity of MDMA to distal axotomy, since only fine serotonergic axons ascending from the raphe nucleus are lost without apparent damage to their cell bodies. However, this axotomy has never been visualized directly in vivo. The present study examined the axonal integrity of the efferent projections from the midbrain raphe nucleus after MDMA exposure using in vivo manganese-enhanced magnetic resonance imaging (MEMRI). Rats were injected subcutaneously six times with MDMA (5 mg/kg) or saline once daily. Eight days after the last injection, manganese ions (Mn2+) were injected stereotactically into the raphe nucleus, and a series of MEMRI images was acquired over a period of 38 h to monitor the evolution of Mn2+-induced signal enhancement across the ventral tegmental area, the medial forebrain bundle (MFB), and the striatum. The MDMA-induced loss of serotonin transporters was clearly evidenced by immunohistological staining consistent with the Mn2+-induced signal enhancement observed across the MFB and striatum. MEMRI successfully revealed the disruption of the serotonergic raphe-striatal projections and the variable effect of MDMA on the kinetics of Mn2+ accumulation in the MFB and striatum.

Postischemic angiogenesis is an important recovery mechanism. Both arteries and veins are upregulated during angiogenesis, but eventually there are more angiogenic veins than arteries in terms of number and length. It is critical to understand how the veins are modulated after ischemia and then transitioned into angiogenic vessels during the proangiogenic stage to finally serve as a restorative strength to the injured area. Using a rat model of transient focal cerebral ischemia, the hypercapnic blood oxygen level-dependent (BOLD) response was used to evaluate vascular reactivity, while the hyperoxic BOLD and tissue oxygen level-dependent (TOLD) responses were used to evaluate the vascular functionality at 1, 3, and 7days after ischemia. Vessel-like venous signals appeared on R2* maps on days 3 and 7, but not on day 1. The large hypercapnic BOLD responses on days 3 and 7 indicated that these areas have high vascular reactivity. The temporal correlation between vascular reactivity and the immunoreactivity to desmin and VEGF further indicates that the integrity of vascular reactivity is associated with the pericyte coverage as regulated by the VEGF level. Vascular functionality remained low on days 1, 3, and 7, as reflected by the small hyperoxic BOLD and large hyperoxic TOLD responses, indicating the low oxygen consumption of the ischemic tissues. These functional changes in proangiogenic veins may be critical for angiogenesis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The Hoffa fat pad (infrapatellar fat pad) is a source of post-traumatic anterior knee pain, and Hoffa disease is a syndrome leading to chronic inflammation of the fat pad. Herein, change in T2* relaxation time of the fat pad was measured in a rodent anterior cruciate ligament transection (ACLX) model in order to (i) examine the causal relationship of anterior cruciate ligament (ACL) deficiency and Hoffa disease and (ii) demonstrate the feasibility of using T2* as an imaging biomarker to monitor disease progression. Three groups of male Sprague Dawley rats (n = 6 each group), received either (i) no intervention; (ii) sham surgery at the right knee; or (iii) right ACLX. T2* relaxation time was measured and histology was examined in the Hoffa fat pad after surgery. At 13 and 18 weeks after surgery, T2* values were significantly higher in the right fat pad than the left (p < 0.001) and significantly higher in the ACLX group than the control and sham groups (p < 0.001). Histology showed fibrosis and degeneration of adipocytes in the right knees of the ACLX group. We conclude that ACL deficiency and Hoffa disease are causally related and that MRI T2* value can serve as an imaging biomarker of Hoffa disease progression., (© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The ability to evaluate the cerebral microvascular structure and function is crucial for investigating pathological processes in brain disorders. Previous angiographic methods based on blood oxygen level-dependent (BOLD) contrast offer appropriate visualization of the cerebral vasculature, but these methods remain to be optimized in order to extract more comprehensive information. This study aimed to integrate the advantages of BOLD MRI in both structural and functional vascular assessments. The BOLD contrast was manipulated by a carbogen challenge, and signal changes in gradient-echo images were computed to generate ΔR2* maps. Simultaneously, a functional index representing the regional cerebral blood volume was derived by normalizing the ΔR2* values of a given region to those of vein-filled voxels of the sinus. This method is named 3D gas ΔR2*-mMRA (microscopic MRA). The advantages of using 3D gas ΔR2*-mMRA to observe the microvasculature include the ability to distinguish air-tissue interfaces, a high vessel-to-tissue contrast, and not being affected by damage to the blood-brain barrier. A stroke model was used to demonstrate the ability of 3D gas ΔR2*-mMRA to provide information about poststroke revascularization at 3 days after reperfusion. However, this technique has some limitations that cannot be overcome and hence should be considered when it is applied, such as magnifying vessel sizes and predominantly revealing venous vessels.

Background: There is an emerging interest in using magnetic resonance imaging (MRI) T2* measurement for the evaluation of degenerative cartilage in osteoarthritis (OA). However, relatively few studies have addressed OA-related changes in adjacent knee structures. This study used MRI T2* measurement to investigate sequential changes in knee cartilage, meniscus, and subchondral bone marrow in a rat OA model induced by anterior cruciate ligament transection (ACLX)., Materials and Methods: Eighteen male Sprague Dawley rats were randomly separated into three groups (n = 6 each group). Group 1 was the normal control group. Groups 2 and 3 received ACLX and sham-ACLX, respectively, of the right knee. T2* values were measured in the knee cartilage, the meniscus, and femoral subchondral bone marrow of all rats at 0, 4, 13, and 18 weeks after surgery., Results: Cartilage T2* values were significantly higher at 4, 13, and 18 weeks postoperatively in rats of the ACLX group than in rats of the control and sham groups (p<0.001). In the ACLX group (compared to the sham and control groups), T2* values increased significantly first in the posterior horn of the medial meniscus at 4 weeks (p = 0.001), then in the anterior horn of the medial meniscus at 13 weeks (p<0.001), and began to increase significantly in the femoral subchondral bone marrow at 13 weeks (p = 0.043)., Conclusion: Quantitative MR T2* measurements of OA-related tissues are feasible. Sequential change in T2* over time in cartilage, meniscus, and subchondral bone marrow were documented. This information could be potentially useful for in vivo monitoring of disease progression.

Understanding of structural and functional characteristics of the vascular microenvironment in gliomas and the impact of antiangiogenic treatments is essential for developing better therapeutic strategies. Although a number of methods exist in which this process can be studied experimentally, no single noninvasive test has the capacity to provide information concerning both microvascular function and morphology. The purpose of present study is to demonstrate the feasibility of using a novel three-dimensional ΔR2-based microscopic magnetic resonance angiography (3D ΔR2-μMRA) technique for longitudinal imaging of tumor angiogenesis and monitoring the effects of antiangiogenic treatment in rodent brain tumor models. Using 3D ΔR2-μMRA, a generally consistent early pattern of vascular development in gliomas was revealed, in which a single feeding vessel was visualized first (arteriogenesis), followed by sprouting angiogenesis. Considerable variability of the tumor-associated vasculature was then noted at later stages of tumor evolution. ΔR2-μMRA revealed that anti-vascular endothelial growth factor treatment induced a rapid and significant alteration of the intratumoral angiogenic phenotype. In summary, 3D ΔR2-μMRA enables high-resolution visualization of tumor-associated vessels while simultaneously providing functional information on the tumor microvasculature. It can serve as a useful tool for monitoring both the temporal evolution of tumor angiogenesis and the impact of antiangiogenic therapies.

Signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) is strongly expressed in extremely invasive lung carcinoma. We showed in our previous study that SCUBE3 triggers the transforming growth factor-β pathway and subsequently promotes tumor angiogenesis and the epithelial-mesenchymal transition (EMT). However, the role of SCUBE3 in early tumor expansion hasn't been fully demonstrated in vivo. The present study used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to temporally assess tumor angiogenesis in SCUBE3-knockdown and control non-small-cell lung carcinoma (NSCLC) cancer cells in the early tumor stage (weeks 1-3). We further evaluated the metastatic potential of the SCUBE3-knockdown and control tumor cells using a circulating tumor cell (CTC) assay. The differences in gene expression profile between these cell lines were determined using microarray analysis. The results show that SCUBE3 knockdown was associated with lower vascular permeability in the tumor and effectively inhibited the metastatic potential of NSCLC, as evidenced by the decreased CTCs in the mice bearing SCUBE3-knockdown tumors. Microarray analysis revealed that several genes involved in angiogenesis and EMT were down-regulated in SCUBE3-knockdown tumors, including matrix metalloproteinases (MMPs) 2, 9, and 14, (MMP-2, MMP-9, and MMP-14, respectively), fibronectin (FN-1), lysyl oxidase (LOX), hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1), early growth response protein 1 (EGR1), and interleukin 8 (IL-8). Together these data suggest that SCUBE3 is a potential target for pharmacological intervention. The findings of the present study also show that differences in vascular permeability precede the CTCs detection, indicating that DCE-MRI may be a sensitive biomarker for assessing tumor invasiveness.

A tri-copolymer sponge consisting of gelatin, hyaluronic acid, and chondroitin sulfate (GHC) was designed to mimic the cartilage environment in vivo for cartilage regeneration. The present study aimed to temporally characterize the magnetic resonance relaxation time of GHC constructs in vivo in a rodent heterotopic model. GHC sponges with cells (GHCc) or without cells (GHC) implanted in rat leg muscle were monitored using MRI (4.7 T MR scanner) on day 0, 7, 14, and 21 after implantation. The results revealed that the transverse relaxation time (T2) of GHC constructs decreased significantly over time when compared to the T2 of GHCc constructs. However, the longitudinal relaxation time (T1) of GHCc and GHC constructs remained stable. Moreover, hematoxylin and eosin and immunohistochemical staining with antibodies to S100 protein, and types I and II collagen showed that normal morphology, phenotype, and function of chondrocytes were preserved in the GHCc construct. Thus, we concluded that GHC constructs adequately support chondrocyte growth and function. On top of that, T2 may be a useful tool for monitoring cartilage regeneration in GHC constructs., (Copyright © 2012 Wiley Periodicals, Inc.)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin commonly used to produce an animal model of Parkinson's disease. Previous studies have suggested a critical role for neuronal nitric oxide (NO) synthase- (nNOS-) derived NO in the pathogenesis of MPTP. However, NO activity is difficult to assess in vivo due to its extremely short biological half-life, and so in vivo evidence of NO involvement in MPTP neurotoxicity remains scarce. In the present study, we utilized flow-sensitive alternating inversion recovery sequences, in vivo localized proton magnetic resonance spectroscopy, and diffusion-weighted imaging to, respectively, assess the hemodynamics, metabolism, and cytotoxicity induced by MPTP. The role of NO in MPTP toxicity was clarified further by administering a selective nNOS inhibitor, 7-nitroindazole (7-NI), intraperitoneally to some of the experimental animals prior to MPTP challenge. The transient increase in cerebral blood flow (CBF) in the cortex and striatum induced by systemic injection of MPTP was completely prevented by pretreatment with 7-NI. We provide the first in vivo evidence of increased nNOS activity in acute MPTP-induced neurotoxicity. Although the observed CBF change may be independent of the toxicogenesis of MPTP, this transient hyperperfusion state may serve as an early indicator of neuroinflammation.

The successful translation of stem-cell therapies requires a detailed understanding of the fate of transplanted cells. Magnetic resonance imaging (MRI) has provided a noninvasive means of imaging cell dynamics in vivo by prelabeling cell with T(2) shortening iron oxide particles. However, this approach suffers from a gradual loss of sensitivity since active cell mitosis could decrease the cellular contrast agent (CA) concentration below detection level. In addition, the interpretation of images may be confounded by hypointensities induced by factors other than this CA susceptibility effect (CASE). We therefore examined the feasibility of exploiting the phase information in MRI to increase the sensitivity of cellular imaging and to differentiate the CASE from endogenous image hypointensity. Phase aliasing and the B(0) field inhomogeneity effect were removed by applying a reliable unwrapping algorithm and a high-pass filter, respectively, thus delineating phase variations originating from high spatial frequencies due to the CASE. We found that the filtered phase map detects labeled cells with high sensitivity and can readily differentiate the cell migration track from the white matter, both of which are hypointense in T(2)-weighted magnitude images. Furthermore, an approximate fivefold contrast-to-noise ratio enhancement can be achieved with an MRI phase map over conventional T(2)-weighted magnitude images., (Copyright © 2012 Elsevier Inc. All rights reserved.)