Significant Difference In Signal Intensity Research Articles

Abstract 1858: Enhanced delivery of anti PD-1 antibody to liver tumors in oncopig using pressure enabled drug delivery (PEDD) versus a systemic delivery

Abstract Background: Anti-PD-1 checkpoint inhibitors have been developed to mitigate immune suppression by reversing T cell exhaustion. Typically, checkpoint inhibitors are delivered systemically, which may be inadequate due to poor drug distribution and limited penetration into solid tumors due to high intra-tumoral pressure. In such tumors, interstitial fluid pressure and solid stress restricts blood flow and therapeutic agent distribution throughout the tumor stroma. Pressure enabled drug deliveryTM (PEDDTM) has been demonstrated to improve therapeutic delivery in pre-clinical models and in patients. PEDD has also been shown to reduce off-target tissue exposure to embolics while increasing intra-tumoral therapeutic concentration. We hypothesized that PEDD hepatic arterial infusion (HAI) using a TriNav device would enhance anti-PD-1 antibody delivery to porcine liver tumors when compared to systemic delivery. Methods: The study was conducted in transgenic pigs (oncopigs) 35-50kg in weight. Explanted liver tissue was treated to induce oncogene expression and re-implanted in the liver at 4 locations for tumor formation. A fixed dosage (1 mg/animal) of fluorescently labeled InVivoSIM anti-human PD-1 (AB_2894731) checkpoint inhibitor (CPI) was infused in 10ml of PBS at 2 ml/min. The TriNav was positioned within a HA branch supplying a hepatic lobe with a fully formed tumor for local-regional infusion. Systemic infusion was conducted through the femoral vein. Liver tissue was collected 1 hour following infusion and drug levels were quantified by nearIR fluorescence imaging on sequential 1 cm thick sections. NearIR images were overlaid on color images, tumor border delineated, and the mean fluorescent CPI signal was calculated in concentric rings relative to the tumor border. Results: A significant 2.6-to-5.4-fold increase in CPI signal intensity was observed from 15mm within the tumor to 30mm from the outer edge of tumor with PEDD using the TriNav device when compared to systemic delivery (p ≤ 0.05). PEDD delivery also resulted in significant 2.5-to-3.9-fold enrichment from 5mm within the tumor to 10mm surrounding the tumor (relative to normal tissue within the treated lobe, p ≤ 0.05). No significant difference in signal intensity was observed in peri-tumoral regions and a reduction in signal was observed in tissues 5mm to 15mm within the tumor relative to normal tissue (p ≤ 0.05) following systemic CPI infusion. Conclusions: This study demonstrates that HAI delivery of CPI into liver tumors in the oncopig via PEDD using a TriNav device resulted in superior delivery compared to systemic infusion. Importantly, PEDD significantly concentrated delivery of CPI into the tumors and within the rapidly growing margin of the tumors where target immune cells such as lymphocytes are present. Citation Format: David Benjamin Jaroch, Chandra C. Ghosh, Prajna Guha, Steven Katz, Bryan F. Cox, Thomas G. Hullinger. Enhanced delivery of anti PD-1 antibody to liver tumors in oncopig using pressure enabled drug delivery (PEDD) versus a systemic delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1858.

Tissue Age Affects Antigenicity and Scoring for the 22C3 Immunohistochemistry Companion Diagnostic Test

Programmed death-ligand 1 (PD-L1) antibody 22C3 is the approved companion diagnostic immunohistochemistry test for treatment with pembrolizumab and cemiplimab in multiple cancer types. The 22C3 and 28-8 antibodies target the extracellular domain (ECD) of PD-L1, which is known to contain N-glycosylation sites. We hypothesize that antigenicity could be affected by the degradation of the glycan part of the epitope and thus change the scoring of the assay over time. Here, we test samples over time and assess the effects of time and deglycosylation on PD-L1 signal by comparing an antibody with an ECD antigen to an antibody with an intracellular domain (ICD) antigen. Ten whole-tissue sections of non–small-cell lung cancer (NSCLC) from 2018 were selected for testing. Fresh-cut serial sections for each case were stained on DAKO Link48 for 22C3 according to the label. In parallel, a previously described laboratory-developed test using E1L3N (an ICD antibody) was performed on the Leica BondRX. Tumor proportion scores for 22C3 and E1L3N were read by a pathologist and compared to the previous clinical diagnoses. To determine the effect using a quantitative approach, a tissue microarray (TMA) cohort with 90 NSCLC cases was similarly assessed. Finally, to determine whether the possible effect of epitope glycosylation, antibodies were tested before and after enzymatic deglycosylation of specimens. We found that 6 of 7 archival positive samples showed a significant reduction in positive staining with 22C3 compared to the original diagnostic sample assessed 3 years earlier. In an older archival TMA cohort, a quantitative significant difference in signal intensity was noted when staining with 22C3 was compared to E1L3N. This loss of signal was not noted in the fresh cell line TMA consistent with a time-dependent degradation of staining. Finally, quantitative assessment of the fresh TMA showed a significant loss of signal after a deglycosylation procedure when stained with 22C3, which was not seen when stained with E1L3N. We believe that these data show that the glycan part of the 22C3 epitope is not stable over time, and that this issue should be considered when assessing archival tissue for diagnostic or research purposes.

MRI parameters for predicting the effect of ultrasound-guided high-intensity focused ultrasound in the ablation of uterine fibroids

To study the value of magnetic resonance imaging (MRI) parameters in predicting the efficacy of ultrasonic ablation of fibroids. A total of 91 patients were divided into groups based on non-perfused volume (NPV) ratio and blood supply type. The preoperative MRI parameters were measured and analysed. A correlation analysis between the MRI parameters and the NPV ratio was performed. Receiver operating characteristic (ROC) curves were used to analyse and determine the cut-off value of MRI parameters to predict the ablation rate of fibroids. The uterine fibroids group with an NPV ratio <80% and the group with an NPV ratio of ≥80% had significant differences in signal intensity (SI) at MRI T2-weighted imaging (WI), fibroid-to-rectus abdominis SI ratio (SIR) at T2WI, and blood supply type (p<0.05). There were no significant differences in fibroid volume, T2WI signal uniformity, and apparent diffusion coefficient (ADC) values. The ADC value and SI and SIR at MRI T2WI in the group with poor blood supply were lower than those in the group with a rich blood supply (p<0.05). SI at MRI T2WI correlated negatively with the NPV ratio. The cut-off values for SI and SIR at MRI T2WI of fibroids whose NPV ratio exceeds 80% were 220.58 and 1.315, respectively. SI at MRI T2WI and blood supply type could be predictors of the efficacy of ablation. Ultrasonic ablation of fibroids with MRI T2WI hyperintensity and a rich blood supply had poor efficacy.

Decoding point‐light displays and fully visible hand grasping actions within the action observation network

Action observation typically recruits visual areas and dorsal and ventral sectors of the parietal and premotor cortex. This network has been collectively termed as extended action observation network (eAON). Within this network, the elaboration of kinematic aspects of biological motion is crucial. Previous studies investigated these aspects by presenting subjects with point‐light displays (PLDs) videos of whole‐body movements, showing the recruitment of some of the eAON areas. However, studies focused on cortical activation during observation of PLDs grasping actions are lacking. In the present functional magnetic resonance imaging (fMRI) study, we assessed the activation of eAON in healthy participants during the observation of both PLDs and fully visible hand grasping actions, excluding confounding effects due to low‐level visual features, motion, and context. Results showed that the observation of PLDs grasping stimuli elicited a bilateral activation of the eAON. Region of interest analyses performed on visual and sensorimotor areas showed no significant differences in signal intensity between PLDs and fully visible experimental conditions, indicating that both conditions evoked a similar motor resonance mechanism. Multivoxel pattern analysis (MVPA) revealed significant decoding of PLDs and fully visible grasping observation conditions in occipital, parietal, and premotor areas belonging to eAON. Data show that kinematic features conveyed by PLDs stimuli are sufficient to elicit a complete action representation, suggesting that these features can be disentangled within the eAON from the features usually characterizing fully visible actions. PLDs stimuli could be useful in assessing which areas are recruited, when only kinematic cues are available, for action recognition, imitation, and motor learning.

Investigation of Changing Imaging Contrast Using Compressed Sensing in Gd-EOB-DTPA Hepatocyte Phase

In recent years, gadolinium ethoxybenzyl diethylenetriamine pantaacetic acid (Gd-EOB-DTPA) has been commonly used in magnetic resonance imaging (MRI) for liver contrast studies. The purpose of this study was to investigate the effect of Hyper SENSE factor on contrast in the Gd-EOB-DTPA hepatocyte phase. The subjects were 21 patients [16 males and 5 females, aged 50-94 years (mean age 68±12years)] who underwent hepatic contrast-enhanced MRI with Gd-EOB-DTPA from March 2021 to December 2021. The contrast ratios (CRs) of liver/spleen and liver/tumor were measured when the Hyper SENSE factor was changed to 1.0, 1.4 and 1.8. As a result, there was no statistically significant difference in signal intensity and CR with the change in the Hyper SENSE factor. In this study, the acquisition time can be shortened without decreasing the CR; therefore, it was suggested to improve MR images to avoid motion artifact.

MRA of the Supraaortic Vasculature: Comparison of Gadobutrol and Gadoterate Meglumine at 1.5 T.

Gadobutrol (GB) and gadoterate meglumine (GM) are contrast agents used for contrast-enhanced magnetic resonance angiography (CEMRA). Supraaortic vasculature (SAV) CEMRAs are used to evaluate stroke risk and neurologic symptoms. There is a need to compare the SAV CEMRA image quality obtained with GB and GM. To intra-individually compare MRA images obtained with equimolar GB and GM at 1.5T in the SAV. Prospective, crossover. Twenty-eight subjects (54 ± 13 years; 17 female). 1.5 T; three-dimensional (3D) gradient recalled echo. Quantitative image quality was measured by normalized signal intensity (SIn ) [SIn =SI blood/SD blood] and contrast ratio (CR) [CR=SI blood/SI muscle], determined by an observer (JWC) with 1 year of vascular imaging experience. Three radiologists (AS, PA, and MU) with (5, 5, and 6 years of) vascular imaging experience evaluated image quality by Likert-scale ratings (of image impression, wall conspicuity, and artifact absence). SIn and CR were compared with paired t-tests or Wilcoxon signed-rank tests and Bland-Altman plots. Qualitative ratings were compared with Wilcoxon signed-rank test. No significant difference in SIn was found between GB and GM. CRs with GB were significantly higher than GM at the right common carotid (6.9 ± 2.5 vs. 4.8 ± 1), left internal carotid (7.3 ± 2 vs. 4.4 ± 1.2), right internal carotid (7.7 ± 2.2 vs. 5 ± 1.1), and left vertebral (6.6 ± 2.2 vs. 4.5 ± 1.1) arteries. Bland-Altman plots showed relatively greater differences between GB and GM at higher CRs and SIn s. GM showed significantly higher artifact than GB (3.56 ± 0.52 vs. 3.36 ± 0.46) and significantly lower overall image quality (10.73 ± 1.45 vs. 11.26 ± 1.58) at the left vertebral artery. At 1.5T and equimolar demonstration, GB (0.1mL/kg, i.e., 0.1 mmol/kg) showed higher CRs in the SAV compared to GM (0.2mL/kg, i.e., 0.1 mmol/kg) at most vessels. Subjective image quality was not significantly different between the two agents for most vessels. 2 TECHNICAL EFFICACY: Stage 2.

Longitudinal Bottom-Up Proteomics of Serum, Serum Extracellular Vesicles, and Cerebrospinal Fluid Reveals Candidate Biomarkers for Early Detection of Glioblastoma in a Murine Model.

Glioblastoma Multiforme (GBM) is a brain tumor with a poor prognosis and low survival rates. GBM is diagnosed at an advanced stage, so little information is available on the early stage of the disease and few improvements have been made for earlier diagnosis. Longitudinal murine models are a promising platform for biomarker discovery as they allow access to the early stages of the disease. Nevertheless, their use in proteomics has been limited owing to the low sample amount that can be collected at each longitudinal time point. Here we used optimized microproteomics workflows to investigate longitudinal changes in the protein profile of serum, serum small extracellular vesicles (sEVs), and cerebrospinal fluid (CSF) in a GBM murine model. Baseline, pre-symptomatic, and symptomatic tumor stages were determined using non-invasive motor tests. Forty-four proteins displayed significant differences in signal intensities during GBM progression. Dysregulated proteins are involved in cell motility, cell growth, and angiogenesis. Most of the dysregulated proteins already exhibited a difference from baseline at the pre-symptomatic stage of the disease, suggesting that early effects of GBM might be detectable before symptom onset.

Origami chips: Development and validation of a paper-based Lab-on-a-Chip device for the rapid and cost-effective detection of 4-methylmethcathinone (mephedrone) and its metabolite, 4-methylephedrine in urine

4-methylmethcathinone (mephedrone) has emerged in drug seizures as a new psychoactive substance (NPS) causing a public health risk of global concern. Currently, there are no commercial microfluidic devices for the selective detection of mephedrone and so this study presents a simple, low-cost and portable paper-based Lab-on-a-Chip (LOC) device with colorimetric detection to fill this gap. Limits of detection for mephedrone in spiked urine and dissolved powder (aqueous) samples are clinically relevant at 4.34 ng mL−1 and 2.51 ng mL−1 respectively. No cross-reactivity for commonly encountered cutting agents, interferents and adulterants were detected. Mephedrone and its main metabolite were detectable in aqueous and urine samples within 3 min. Stability and reproducibility measurements showed no significant difference in signal intensity over eight weeks and no significant difference within or between devices. The proposed device has the potential to provide cost-effective, rapid, on-site testing within forensic or clinical settings and therefore has wide global applicability.

Analysis of correlation between magnetic resonance imaging features and prognosis of invasive pituitary adenoma

Objective: To explore the application of conventional nuclear magnetic resonance imaging, diffusion-weighted imaging and dynamic contrast-enhanced imaging in invasive pituitary adenoma, and to study the correlation between its imaging features and prognosis. Methods: The imaging manifestations (including T1WI, T2WI, ADC and dynamic contrast-enhanced MR), clinical features and pathological data of 47 cases of invasive pituitary adenomas (IPA) in Tianjin Huanhu Hospital from June 2017 to June 2018 were retrospectively analyzed, and compared with 16 cases of non-invasive pituitary adenoma (NIPA). The differences in tumor/white matter signal intensity ratio on T1WI and T2WI images, MR signs, ADC values and time signal-curve type, peak enhancement time and average enhancement rate between the two groups were observed. Postoperative MR enhanced scan and related hormone results were reviewed to evaluate the prognosis of all patients. Logistic stepwise regression analysis was used to analyze the relationship between IPA imaging characteristics and prognosis. Results: The location, shape, size, Knosp classification and ADC value of tumors were significantly different between IPA and NIPA groups (χ(2) values were 41.344, 21.818, 28.596 respectively, t values were 5.869, 11.720 respectively, all P<0.05). The majority of T1WI, T2WI and enhanced heterogeneous signals occurred in IPA group (P<0.05). IPA showed two-stage enhancement characteristics of rapid enhancement and fast subsidence phase. There were significant differences in peak enhancement time between intrasellar tumors and invasive cavernous sinus tumors. There were no significant differences in signal intensity of T1 and diffusion limitation and two-stage enhancement characteristics between the two groups (all P>0.05). There was a significant correlation between the ratio of tumor body/white matter signal on T2WI, ADC value and the constitution of invasive pituitary tumors (all P<0.05). In IPA, 9 cases(19%) were totally resected, 25 cases(53%) subtotally resected and 13 cases(28%) partially resected. Postoperative symptoms were improved in 29 cases(62%), alleviated in 6 cases(13%), unhealed in 3 cases(6%), assisted drug therapy in 7 cases and radiotherapy in 15 cases. All cases were followed up for 7 to 16 months, with a median time of 12.5 months. Eight cases recurred, with a recurrence rate of 17%. There were significant differences in the total/subtotal resection rate, the improvement rate of symptoms and the need for adjuvant treatment among IPA with different texture (all P<0.05).Knosp grade, tumor size and the ratio of tumor body to white matter on T2WI were associated with IPA recurrence (all P<0.05). Conclusion: It is helpful to diagnose IPA by analyzing the distribution, shape, size, ADC value and signal difference of tumors in sella turcica region through MR and DWI signs. Combined with dynamic contrast enhancement features, the invasion of IPA and its surrounding tissues can be early judged, and the texture of the tumors can be assessed by imaging signs, so as to better evaluate the therapeutic effect and prognosis of IPA.

Characterization of Volatile Organic Compounds of Healthy and Huanglongbing-Infected Navel Orange and Pomelo Leaves by HS-GC-IMS.

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, is the only natural vector of bacteria responsible for Huanglongbing (HLB), a worldwide destructive disease of citrus. ACP reproduces and develops only on the young leaves of its rutaceous host plants. Olfactory stimuli emitted by young leaves may play an important role in ACP control and HLB detection. In this study, volatile organic compounds (VOCs) from healthy and HLB-infected young leaves of navel orange and pomelo were analyzed by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS). A total of 36 compounds (including dimers or polymers) were identified and quantified from orange and 10 from pomelo leaves. Some compounds showed significant differences in signal intensity between healthy and HLB-infected leaves and may constitute possible indicators for HLB infection. Principal component analysis (PCA) clearly discriminated healthy and HLB-infected leaves in both orange and pomelo. HS-GC-IMS was an effective method to identify VOCs from leaves. This study may help develop new methods for detection of HLB or find new attractants or repellents of ACP for prevention of HLB.

Is Full Endoscopic Lumbar Discectomy Less Invasive Than Conventional Surgery? A Randomized MRI Study

In the present randomized prospective study, we compared the surgical invasiveness using a quantitative volumetric analysis of postoperative paravertebral muscle signal intensity changes between transforaminal full endoscopic lumbar discectomy (FELD) and open discectomy (OD). We prospectively collected the data from 50 patients with a single-level lumbar foraminal herniation, invalidating radicular pain, and adequate imaging studies available (postoperative magnetic resonance imaging [MRI] <24 hours). These patients had been randomly assigned to FELD (n= 25) or OD (n= 25). Data were collected on age, sex, leg and back pain, complications, and follow-up time. Muscle segmentations were performed manually using 3DSlicer software on postoperative isovolumetric T1-weighted contrast-enhanced and T2-weighted short tau inversion recovery MRI scans. Both sequences were processed using multiplanar reconstruction in orthogonal planes. The clinical and demographic characteristics and volumetric data were then compared between the 2 groups. We found a higher mean volume of paravertebral muscle signal alterations among the OD-treated patients in both T2-weighted short tau inversion recovery MRI (P ≤ 0.001) and T1-weighted contrast-enhanced MRI (P≤ 0.001) scans than among the FELD-treated patients. No differences were found between the median preoperative and postoperative leg pain between the 2 groups (P=1.000). The median scores for postoperative back pain were significantly lower for the FELD group (P ≤ 0.001), as was the median interval from surgery to autonomous mobilization (P= 0.001). We found a significant difference in signal intensity of the paravertebral muscles between the FELD and OD groups, reflective of the minor surgical invasiveness of endoscopic discectomy. FELD resulted in less trauma to the paraspinal muscles, possibly also reducing inflammatory cytokine release and, therefore, is a valuable tool for spinal surgeons.

Distribution Analysis of Salvianolic Acids in Myocardial Ischemic Pig Tissues by Automated Liquid Extraction Surface Analysis Coupled with Tandem Mass Spectrometry.

The distribution of active compounds of traditional Chinese medicine Salvia miltiorrhiza Bunge (Chinese name: Danshen) in vivo was determined by establishing a liquid extraction surface analysis coupled with the tandem mass spectrometry (LESA-MS/MS) method. Stability analysis and distribution analysis were designed in the present study using normal animals or a myocardial ischemia model. The model assessment was performed four weeks after surgery, and then three groups were created: a normal-dose group, a model-blank group, and a model-dose group. Meanwhile, Danshen decoction administration began in dose groups and lasted for four weeks. In stability analysis, four salvianolic acids—Danshensu (DSS), caffeic acid (CAA), rosmarinic acid (RA), and salvianolic acid A (SAA)—in kidney tissues from the normal-dose group were detected by LESA-MS/MS under four conditions, and then distribution analysis was conducted in different tissues using the same method. Ejection fraction (EF) and fractional shortening (FS) in animals from two model groups decreased significantly four weeks after surgery (P < 0.01) and were improved after four weeks of Danshen decoction administration (P < 0.01). Results of stability analysis demonstrated that this method was basically stable since there were no significant differences in signal intensities of DSS, CAA, and SAA under four conditions (P > 0.05). Distribution analysis showed the signal intensities of DSS in the liver and kidney and SAA in the heart were higher in the model-dose group than in the normal-dose group (P < 0.05 or P < 0.01). Signal intensities of RA in the liver and kidney, and SAA in the liver were lower in the model-dose group compared with the normal-dose group (P < 0.05 or P < 0.01). In conclusion, Danshen decoction has the effect of improving the ischemic condition in a chronic myocardial ischemia model, and the content of two active compounds increased in the targets. These findings contribute to an understanding of the therapeutic role of Danshen in cardiovascular disease.

Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the Brain: Overlooked and Misinterpreted.

The "glymphatic system" (GS), a brain-wide network of cerebrospinal fluid microcirculation, supplies a pathway through and out of the central nervous system (CNS); malfunction of the system is implicated in a variety of neurological disorders. In this exploratory study, we analyzed the potential of a new imaging approach that we coined delayed T2-weighted gadolinium-enhanced imaging to visualize the GS in vivo. Heavily T2-weighted fluid-attenuated inversion recovery (hT2w-FLAIR) magnetic resonance imaging was obtained before, and 3 hours and 24 hours after intravenous gadolinium-based contrast agent (GBCA) application in 33 neurologically healthy patients and 7 patients with an impaired blood-brain barrier (BBB) due to cerebral metastases. Signal intensity (SI) was determined in various cerebral fluid spaces, and white matter hyperintensities were quantified by applying the Fazekas scoring system. Delayed hT2w-FLAIR showed GBCA entry into the CNS via the choroid plexus and the ciliary body, with GBCA drainage along perineural sheaths of cranial nerves and along perivascular spaces of penetrating cortical arteries. In all patients and all sites, a significant SI increase was found for the 3 hours and 24 hours time points compared with baseline. Although no significant difference in SI was found between neurologically healthy patients and patients with an impaired BBB, a significant positive correlation between Fazekas scoring system and SI increase in the perivascular spaces 3 hours post injection was shown. Delayed T2-weighted gadolinium-enhanced imaging can visualize the GBCA pathway into and through the GS. Presence of GBCAs within the GS might be regarded as part of the natural excretion process and should not be mixed up with gadolinium deposition. Rather, the correlation found between deep white matter hyperintensities, an imaging sign of vascular dementia, and GS functioning demonstrated feasibility to exploit the pathway of GBCAs through the GS for diagnostic purposes.

Gadolinium contrast medium administration does not adversely affect T2*-weighted gradient recalled echo magnetic resonance imaging of the canine brain at 1.5 Tesla.

As gadolinium-based contrast agents are paramagnetic and have T2 shortening effects, they have the potential to adversely affect gradient recalled echo sequences. The aim of this prospective, cross-sectional study was to evaluate the effects of gadolinium administration on T2*-weighted sequence diagnostic quality and signal intensity when imaging the canine brain. A total of 100 dogs underwent brain magnetic resonance imaging (MRI) including pre- and postcontrast T2*-weighted sequences acquired with a delay (Group A) or immediately (Group B) following gadolinium administration. Pre- and postcontrast images were subjectively compared. In dogs with intracranial enhancing masses, regions of interest were drawn on corresponding images and signal intensity ratios were calculated. The effect of degree and pattern of contrast enhancement, susceptibility artifacts, and time between contrast injection and T2*-weighted sequence acquisition on signal intensity ratio was evaluated. Overall 31 dogs had contrast enhancing intracranial masses. Subjectively, there was no difference in image quality of T2*-weighted sequences obtained before and after contrast medium administration. No significant signal intensity differences of intracranial contrast enhancing masses were found (Group A P=0.9999; Group B P=0.9992). Susceptibility artifacts did not differ in appearance, and there was no effect on calculated signal intensity ratio (P=0.8142). Similarly, there was no effect of degree of enhancement or contrast heterogeneity on signal intensity ratio (P=0.4413). No correlation was found between signal intensity ratio and the time to acquisition (P=0.199). Administration of gadolinium-based MRI contrast agents does not adversely affect T2*-weighted imaging of the brain in dogs at 1.5T even in the presence of contrast enhancing lesions.

Evaluation of Gadolinium Deposition in the Brain After MR Arthrography.

Although significant investigation has been done into the deposition of gadolinium in the brains of patients receiving IV gadolinium, there is little research concerning nonintravenous uses of gadolinium, specifically in conjunction with musculoskeletal MR arthrography. Although small in volume, intraarticular administration is an off-label use of gadolinium, necessitating careful scrutiny for patient safety. Thus, we investigated the relationship between intraarticular gadolinium administration during MR arthrography and the presence of intracranial gadolinium deposition on subsequent brain MRI. An institutional review board-approved retrospective study was performed of patients with no history of gadolinium exposure who underwent MR arthrography from 2006 to 2016 followed by an unenhanced brain MRI examination. ROIs were manually placed within bilateral dentate nuclei (DN), bilateral globus pallidi (GP), bilateral thalami, bilateral middle cerebral peduncles (MCP), and the central pons (CP) on T1-weighted sequences. The left and right ROIs were averaged, and ratios of signal intensity were calculated for DN/MCP, DN/CP, GP/MCP, GP/CP, thalamus/MCP, and thalamus/CP. Similar ROIs were placed and ratios calculated for age-matched control subjects who had a history of brain MRI but no prior gadolinium exposure. We used t testing to compare signal intensity ratios between patients and control subjects. A total of 31 patients met the inclusion criteria. We found no significant difference in signal intensity between patients and control subjects for DN/MCP (p = 0.40), DN/CP (p = 0.76), GP/MCP (p = 0.51), GP/CP (p = 0.86), thalamus/MCP (p = 0.93), and thalamus/CP (p = 0.30). No association was found between intraarticular gadolinium administration for MR arthrography and detectable gadolinium deposition within the brain.

Utility of Magnetic Resonance Imaging for Predicting Severity of Sciatic Nerve Injury.

This study aimed to investigate the diagnostic accuracy of magnetic resonance (MR) imaging for categorizing sciatic peripheral nerve injury (PNI) as high-grade (Sunderland grades IV-V) or low-grade (Sunderland grades I-III) PNI. In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, consecutive MR imaging of the pelvis and thighs, performed for the evaluation of traumatic sciatic neuropathy, was reviewed for sciatic nerve signal intensity, size, architectural distortion, bulbous enlargement, perineural fibrosis, discontinuity, and muscle denervation changes. Clinical data, electrodiagnostic testing, and surgical history were used to determine PNI grade (high, low). Descriptive and diagnostic performance statistics were applied. Of 24 patients, there were 12 high-grade and 12 low-grade PNI. There was no significant difference in signal intensity or size between high-grade and low-grade PNI (1.3 ± 0.5 cm vs 0.9 ± 0.3 cm, P = 0.09). The sensitivity and specificity for the presence of individual features in predicting high-grade injury were 83% and 67% for architectural distortion, 58% and 75% for bulbous enlargement, 50% and 83% for perineural fibrosis, 25% and 100% for discontinuity, and 67% and 75% for skeletal muscle denervation changes, respectively. Overall, the sensitivity and specificity of MR imaging for categorizing sciatic PNI as high grade was 75% and 83%, respectively. The MR characterization of PNI severity remains challenging. Useful features indicative of high-grade PNI include bulbous enlargement, perineural fibrosis, muscle denervation changes, and nerve discontinuity.

Evaluation of Rabbit VX2 Tumor Model Using Magnetic Resonance T1-Mapping and T2-Mapping Techniques at 1.5T

Most routine magnetic resonance imaging only investigates morphology differences between normal and abnormal tissues. Magnetic resonance T1 and T2 relaxation times are important indices for evaluating pathological changes in tissue. T1-mapping and T2-mapping techniques can be used to perform quantitative analysis as well as qualitative analysis of tissue characteristics. This study aimed to perform long-term monitoring of the VX2 tumor progression and distribution on New Zealand rabbit thigh tissue using three dimensional T1-weighted (T1W) sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE), T2-weighted (T2W) SPACE, T1-mapping and T2-mapping techniques. The signal intensity (SI), T1 and T2 relaxation times of normal muscle and VX2 tumor were measured to evaluate the tumor characteristics. The nonparametric Mann–Whitney U test results showed that there were significant differences in SIs of T1W SPACE images, SIs of T2W SPACE images, T1 relaxation time and T2 relaxation time at the same day after VX2 implantation between normal tissue and VX2 tumor (p values < 0.05). There were also significant differences in time course average values of SIs of T1W SPACE images, SIs of T2W SPACE images, T1 relaxation time and T2 relaxation time between normal tissue and VX2 tumor (p values < 0.05). T2W SPACE, T1 mapping and T2 mapping were superior to T1W SPACE in the early detection of VX2 tumor. T1 mapping and T2 mapping techniques could be used to evaluate tumor growth and metastasis. T1 and T2 maps might be referenced as biomarkers and predictive indices in the evolution of pathologies.

The value of DCE-MRI in assessing the course of thyroid associated ophthalmopathy

Objective: To explore the feasibility of the semi-quantitative rectus extraocular muscle (EOM) parameters of dynamic contrast-enhanced magetic resonance imaging (DCE-MRI) in assessing the clinical course of thyroid associated ophthalmopathy (TAO). Methods: It was a retrospective case series study. A total of 136 cases of TAO were recruited from March 2011 to October 2012 in the Tianjin the first center hospital including 63 males and 72 females, aged 24.0-65.0 years, with an average age of (40.5±10.9) years. Forty healthy volunteers were recruited as control group (CG). According to clinical activity score (CAS), all TAO patients were divided into 2 groups, activity group (AG) and inactivity group (IAG). MRI and DCE-MRI orbit scan were performed in each subject. Drew time-intensity curves (TIC) by Siemens 3.0 MR (syngo) post-processing workstation. The semi-quantitative parameters of DCE-MRI were calculated. The semi-quantitative paramters based on TIC include early enhancement coefficient (EEC), maximum enhancement coefficient (Emax) and wash-out coefficient (WC(5min)). Kruskal-Wallis H rank test was used for comparing signal intensity among 3 groups, and Nemenyi test for pairwise comparison between groups. The DCE-MRI parameters (EEC, Emax, WC(5 min)) among groups were compared by one-way ANOVA, and Bonferroni t test is for pairwise comparison between groups. The diagnostic value of mean EEC, mean Emax, WC(5min) for assessment of the clinical course in TAO was analyzed by ROC curve. Results: There were significant difference in signal intensity (SI) of rectus EOM on T(2)WI among CG, AG and IAG, which is significantly different in 88 cases of AG including 45 cases of high intensity 51.1%, 23 cases of moderate intensity 26.1%, and 20 cases of low intensity 22.7%,compared with CG and IAG. EEC (P<0.05), Emax and WC5min values of rectus EOM of TAO group were significantly lower than those of CG(P<0.05), which values of rectus EOM of TAO active group of EEC are 0.63±0.06、0.61±0.05、0.56±0.09、0.57±0.09, and values of rectus EOM of TAO inactive group of EEC are 0.49±0.05、0.50±0.08、0.57±0.10、0.55±0.09. The values of rectus EOM of TAO active group of Emax are 1.35±0.09、1.28±0.09、1.21±0.17、1.25±0.10, and the values of rectus EOM of TAO inactive group of Emax are 1.04±0.06、1.05±0.10、1.20±0.19、1.16±0.11. The values of rectus EOM of TAO active group of WC(5 min) are 0.13±0.03、0.13±0.03、0.13±0.06、0.13±0.03 and the values of rectus EOM of TAO inactive group of WC5min are 0.08±0.02、0.79±0.03、0.11±0.06、0.09± 0.03. EEC (χ(2)=9.20, P<0.05), Emax and WC(5min) values of rectus EOM of TAO group were significantly lower than those of CG (P<0.05). EEC, Emax and WC(5min) values of medial rectus and inferior rectus EOM of IAG were significantly lower than those of AG(P<0.05). WC(5min) values of superior rectus EOM of IAG were significantly lower than those of AG (P<0.05). There were no differences in EEC and Emax values of lateral rectus and superior rectus EOM between IAG and AG (P>0.05). There were no differences in WC(5min) values of lateral rectus EOM between IAG and AG (P>0.05). The area under the curve (AUC) were 0.771, 0.879, 0.898 for mean EEC, mean Emax, and mean WC(5min), respectively. Conclusion: The semi-quantitative paramters of DCE-MRI can show the clinical activity of TAO patients and can be considered as the quantitative index of TAO activity staging. (Chin J Ophthalmol, 2017, 53: 430-435).

Peribiliary liver metastases MR findings.

We described magnetic resonance (MR) features of peribiliary metastasis and of periductal infiltrative cholangiocarcinoma. We assessed 35 patients, with peribiliary lesions, using MR 4-point confidence scale. T1-weighted (T1-W), T2-weighted (T2-W) and diffusion-weighted images (DWI) signal intensity, enhancement pattern during arterial, portal, equilibrium and hepatobiliary phase were assessed. We identified 24 patients with periductal-infiltrating cholangiocellular carcinoma. The lesions in 34 patients appeared as a single tissue, while in a single patient, the lesions appeared as multiple individual lesions. According to the confidence scale, the median value was 4 for T2-W, 4 for DWI, 3.6 for T1-W in phase, 3.6 for T1-W out phase, 3 for MRI arterial phase, 3.2 for MRI portal phase, 3.2 for MRI equilibrium phase and 3.6 for MRI hepatobiliary phase. According to Bismuth classification, all lesions were type IV. In total, 19 (54.3%) lesions were periductal, 15 (42.9%) lesions were intraperiductal, and 1 (2.8%) lesion was periductal intrahepatic. All lesions showed hypointense signal in T1-W and in ADC maps and hyperintense signal in T2-W and DWI. All lesions showed a progressive contrast enhancement. There was no significant difference in signal intensity and contrast enhancement among all metastases and among all metastases with respect to CCCs, for all imaging acquisitions (p value >0.05). MRI is the method of choice for biliary tract tumors thanks to the possibility to obtain morphological and functional evaluations. T2-W and DW sequences have highest diagnostic performance. MRI does not allow a correct differential diagnosis among different histological types of metastasis and between metastases and CCC.

Predicting Glioblastoma Recurrence by Early Changes in the Apparent Diffusion Coefficient Value and Signal Intensity on FLAIR Images.

Recurrence of glioblastoma multiforme (GBM) arises from areas of microscopic tumor infiltration that have yet to disrupt the blood-brain barrier. We hypothesize that these microscopic foci of invasion cause subtle variations in the apparent diffusion coefficient (ADC) and FLAIR signal detectable with the use of computational big-data modeling. Twenty-six patients with native GBM were studied immediately after undergoing gross total tumor resection. Within the peritumoral region, areas of future GBM recurrence were identified through coregistration of follow-up MRI examinations. The likelihood of tumor recurrence at each individual voxel was assessed as a function of signal intensity on ADC maps and FLAIR images. Both single and combined multivariable logistic regression models were created. A total of 419,473 voxels of data (105,477 voxels of data within tumor recurrence and 313,996 voxels of data on surrounding peritumoral edema) were analyzed. For future areas of recurrence, a 9.5% decrease in the ADC value (p < 0.001) and a 9.2% decrease in signal intensity on FLAIR images (p < 0.001) were shown, compared with findings for the surrounding peritumoral edema. Logistic regression revealed that the amount of signal loss on both ADC maps and FLAIR images correlated with the likelihood of tumor recurrence. A combined multiparametric logistic regression model was more specific in the prediction of tumor recurrence than was either single-variable model alone. Areas of future GBM recurrence exhibit small but highly statistically significant differences in signal intensity on ADC maps and FLAIR images months before the development of abnormal enhancement occurs. A multiparametric logistic model calibrated to these changes can be used to estimate the burden of microscopic nonenhancing tumor and predict the location of recurrent disease. Computational big-data modeling performed at the voxel level is a powerful technique capable of discovering important but subtle patterns in imaging data.