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The purpose of the present pilot study was to estimate T1 and T2 metric values derived simultaneously from a new, rapid Magnetic Resonance Fingerprinting (MRF) technique, as well as to assess their ability to characterize—brain metastases (BM) and normal-appearing brain tissues. Fourteen patients with BM underwent MRI, including prototype MRF, on a 3T scanner. In total, 108 measurements were analyzed: 42 from solid parts of BM’s (21 each on T1 and T2 maps) and 66 from normal-appearing brain tissue (11 ROIs each on T1 and T2 maps for gray matter [GM], white matter [WM], and cerebrospinal fluid [CSF]). The BM’s mean T1 and T2 values differed significantly from normal-appearing WM (p < 0.05). The mean T1 values from normal-appearing GM, WM, and CSF regions were 1205 ms, 840 ms, and 4233 ms, respectively. The mean T2 values were 108 ms, 78 ms, and 442 ms, respectively. The mean T1 and T2 values for untreated BM (n = 4) were 2035 ms and 168 ms, respectively. For treated BM (n = 17) the T1 and T2 values were 2163 ms and 141 ms, respectively. MRF technique appears to be a promising and rapid quantitative method for the characterization of free water content and tumor morphology in BMs.

The present exploratory study investigates the performance of a new, rapid, synthetic MRI method for diagnostic image quality assessment and measurement of relaxometry metric values in head and neck (HN) tumors and normal-appearing masseter muscle. The multi-dynamic multi-echo (MDME) sequence was used for data acquisition, followed by synthetic image reconstruction on a 3T MRI scanner for 14 patients (3 untreated and 11 treated). The MDME enables absolute quantification of physical tissue properties, including T1 and T2, with a shorter scan time than the current state-of-the-art methods used for relaxation measurements. The vendor termed the combined package MAGnetic resonance imaging Compilation (MAGiC). In total, 48 regions of interest (ROIs) were analyzed, drawn on normal-appearing masseter muscle and tumors in the HN region. Mean T1 and T2 values obtained from normal-appearing muscle were 880 ± 52 ms and 46 ± 3 ms, respectively. Mean T1 and T2 values obtained from tumors were 1930 ± 422 ms and 77 ± 13 ms, respectively, for the untreated group, 1745 ± 410 ms and 107 ± 61 ms, for the treated group. A total of 1552 images from both synthetic MRI and conventional clinical imaging were assessed by the radiologists to provide the rating for T1w and T2w image contrasts. The synthetically generated qualitative T2w images were acceptable and comparable to conventional diagnostic images (93% acceptability rating for both). The acceptability ratings for MAGiC-generated T1w, and conventional images were 64% and 100%, respectively. The benefit of MAGiC in HN imaging is twofold, providing relaxometry maps in a clinically feasible time and the ability to generate a different combination of contrast images in a single acquisition.

Cancer care increasingly relies on imaging for patient management. The two most common cross-sectional imaging modalities in oncology are computed tomography (CT) and magnetic resonance imaging (MRI), which provide high-resolution anatomic and physiological imaging. Herewith is a summary of recent applications of rapidly advancing artificial intelligence (AI) in CT and MRI oncological imaging that addresses the benefits and challenges of the resultant opportunities with examples. Major challenges remain, such as how best to integrate AI developments into clinical radiology practice, the vigorous assessment of quantitative CT and MR imaging data accuracy, and reliability for clinical utility and research integrity in oncology. Such challenges necessitate an evaluation of the robustness of imaging biomarkers to be included in AI developments, a culture of data sharing, and the cooperation of knowledgeable academics with vendor scientists and companies operating in radiology and oncology fields. Herein, we will illustrate a few challenges and solutions of these efforts using novel methods for synthesizing different contrast modality images, auto-segmentation, and image reconstruction with examples from lung CT as well as abdome, pelvis, and head and neck MRI. The imaging community must embrace the need for quantitative CT and MRI metrics beyond lesion size measurement. AI methods for the extraction and longitudinal tracking of imaging metrics from registered lesions and understanding the tumor environment will be invaluable for interpreting disease status and treatment efficacy. This is an exciting time to work together to move the imaging field forward with narrow AI-specific tasks. New AI developments using CT and MRI datasets will be used to improve the personalized management of cancer patients.

Background Patients with human papillomavirus–related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy. Methods In 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia. Patients without hypoxia at baseline or intratreatment received 30 Gy; patients with persistent hypoxia received 70 Gy. Neck dissection was performed at 4 months in deescalated patients to assess pathologic response. Magnetic resonance imaging (weekly), circulating plasma cell-free DNA, RNA-sequencing, and whole-genome sequencing (WGS) were performed to identify potential molecular determinants of response. Samples from an independent prospective study were obtained to reproduce molecular findings. All statistical tests were 2-sided. Results Fifteen of 19 patients had no hypoxia on baseline PET or resolution on intratreatment PET and were deescalated to 30 Gy. Of these 15 patients, 11 had a pathologic complete response. Two-year locoregional control and overall survival were 94.4% (95% confidence interval = 84.4% to 100%) and 94.7% (95% confidence interval = 85.2% to 100%), respectively. No acute grade 3 radiation–related toxicities were observed. Microenvironmental features on serial imaging correlated better with pathologic response than tumor burden metrics or circulating plasma cell-free DNA. A WGS-based DNA repair defect was associated with response (P = .02) and was reproduced in an independent cohort (P = .03). Conclusions Deescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of radiotherapy.

BACKGROUND AND PURPOSE: To determine the ability of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict long-term response of brain metastases prior to and within 72 hours of stereotactic radiosurgery (SRS). METHODS: In this prospective pilot study, multiple b-value DWI and T1-weighted DCE-MRI were performed in patients with brain metastases before and within 72 hours following SRS. Diffusion-weighted (DW) images were analyzed using the monoexponential and intravoxel incoherent motion (IVIM) models. DCE-MRI data were analyzed using the extended Tofts pharmacokinetic model. The parameters obtained with these methods were correlated with brain metastasis outcomes according to modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. RESULTS: We included 25 lesions from 16 patients; 16 patients underwent pre-SRS MRI and 12/16 patients underwent both pre- and early (within 72 hours) post-SRS MRI. The perfusion fraction (f) derived from IVIM early post-SRS was higher in lesions demonstrating progressive disease than in lesions demonstrating stable disease, partial response, or complete response (q = 0.041). Pre-SRS extracellular extravascular volume fraction, v(e), and volume transfer coefficient, k(trans), derived from DCE-MRI were higher in non-responders versus responders (q = 0.041). CONCLUSIONS: Quantitative DWI and DCE-MRI are feasible imaging methods in the pre- and early (within 72 hours) post-SRS evaluation of brain metastases. DWI- and DCE-MRI-derived parameters demonstrated physiologic changes (tumor cellularity and vascularity) and offer potentially useful biomarkers that can predict treatment response. This allows for initiation of alternate therapies within an effective time window that may help prevent disease progression.

The present preliminary study aims to characterize brain metastases (BM) using T1 and T2 maps generated from newer, rapid, synthetic MRI (MAGnetic resonance image Compilation; MAGiC) in a clinical setting. We acquired synthetic MRI data from 11 BM patients on a 3T scanner. A multiple-dynamic multiple-echo (MDME) sequence was used for data acquisition and synthetic image reconstruction, including post-processing. MDME is a multi-contrast sequence that enables absolute quantification of physical tissue properties, including T1 and T2, independent of the scanner settings. In total, 82 regions of interest (ROIs) were analyzed, which were obtained from both normal-appearing brain tissue and BM lesions. The mean values obtained from the 48 normal-appearing brain tissue regions and 34 ROIs of BM lesions (T1 and T2) were analyzed using standard statistical methods. The mean T1 and T2 values were 1143 ms and 78 ms, respectively, for normal-appearing gray matter, 701 ms and 64 ms for white matter, and 4206 ms and 390 ms for cerebrospinal fluid. For untreated BMs, the mean T1 and T2 values were 1868 ms and 100 ms, respectively, and 2211 ms and 114 ms for the treated group. The quantitative T1 and T2 values generated from synthetic MRI can characterize BM and normal-appearing brain tissues.

We aimed to assess longitudinal changes in quantitative imaging metric values obtained from diffusion-weighted (DW-) and dynamic contrast-enhanced magnetic resonance imaging (DCE)-MRI at pre-treatment (TX[0]), immediately after the first fraction of stereotactic body radiotherapy (D1-TX[1]), and 6 weeks post-TX (Post-TX[2]) in patients with pancreatic ductal adenocarcinoma. Ten enrolled patients (n = 10) underwent DW- and DCE-MRI examinations on a 3.0 T scanner. The apparent diffusion coefficient, ADC (mm2/s), was derived from DW imaging data using a monoexponential model. The tissue relaxation rate, R1t, time-course data were fitted with a shutter-speed model, which provides estimates of the volume transfer constant, Ktrans (min−1), extravascular extracellular volume fraction, ve, and mean lifetime of intracellular water protons, τi (seconds). Wilcoxon rank-sum test compared the mean values, standard deviation, skewness, kurtosis, and relative percentage (r, %) changes (Δ) in ADC, Ktrans, ve, and τi values between the magnetic resonance examinations. rADCΔ2–0 values were significantly greater than rADCΔ1-0 values (P = .009). rKtransΔ2–0 values were significantly lower than rKtrans Δ1-0 values (P = .048). rveΔ2-1 and rveΔ2-0 values were significantly different (P = .016). rτiΔ2-1 values were significantly lower than rτiΔ2-0 values (P = .008). For group comparison, the pre-TX mean and kurtosis of ADC (P = .18 and P = .14), skewness and kurtosis of Ktrans values (P = .14 for both) showed a leaning toward significant difference between patients who experienced local control (n = 2) and failed early (n = 4). DW- and DCE-MRI-derived quantitative metrics could be useful biomarkers to evaluate longitudinal changes to stereotactic body radiotherapy in patients with pancreatic ductal adenocarcinoma.

We developed and tested the feasibility of computational fluid modeling (CFM) based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for quantitative estimation of interstitial fluid pressure (IFP) and velocity (IFV) in patients with head and neck (HN) cancer with locoregional lymph node metastases. Twenty-two patients with HN cancer, with 38 lymph nodes, underwent pretreatment standard MRI, including DCE-MRI, on a 3-Tesla scanner. CFM simulation was performed with the finite element method in COMSOL Multiphysics software. The model consisted of a partial differential equation (PDE) module to generate 3D parametric IFP and IFV maps, using the Darcy equation and Ktrans values (min−1, estimated from the extended Tofts model) to reflect fluid influx into tissue from the capillary microvasculature. The Spearman correlation (ρ) was calculated between total tumor volumes and CFM estimates of mean tumor IFP and IFV. CFM-estimated tumor IFP and IFV mean ± standard deviation for the neck nodal metastases were 1.73 ± 0.39 (kPa) and 1.82 ± 0.9 × (10−7 m/s), respectively. High IFP estimates corresponds to very low IFV throughout the tumor core, but IFV rises rapidly near the tumor boundary where the drop in IFP is precipitous. A significant correlation was found between pretreatment total tumor volume and CFM estimates of mean tumor IFP (ρ = 0.50, P = 0.004). Future studies can validate these initial findings in larger patients with HN cancer cohorts using CFM of the tumor in concert with DCE characterization, which holds promise in radiation oncology and drug-therapy clinical trials.

We aimed to compare the geometric distortion (GD) correction performance and apparent diffusion coefficient (ADC) measurements of single-shot diffusion-weighted echo-planar imaging (SS-DWEPI), multiplexed sensitivity encoding (MUSE)-DWEPI, and MUSE-DWEPI with reverse-polarity gradient (RPG) in phantoms and patients. We performed phantom studies at 3T magnetic resonance imaging (MRI) using the American College of Radiology phantom and Quantitative Imaging Biomarker Alliance DW-MRI ice-water phantom to assess GD and effect of distortion in the measurement of ADC, respectively. Institutional review board approved the prospective clinical component of this study. DW-MRI data were obtained from 11 patients with head and neck cancer using these three DW-MRI methods. Wilcoxon signed-rank (WSR) and Kruskal–Wallis (KW) tests were used to compare ADC values, and qualitative rating by radiologist between three DW-MRI methods. In the ACR phantom, GD of 0.17% was observed for the b = 0 s/mm2 image of the MUSE-DWEPI with RPG method compared with that of 1.53% and 2.1% of MUSE-DWEPI and SS-DWEPI, respectively, The corresponding methods root-mean-square errors were 0.58, 3.37, and 5.07 mm. WSR and KW tests showed no significant difference in the ADC measurement between these three DW-MRI methods for both healthy masseter muscles and neoplasms (P &gt, 05). We observed improvement in spatial accuracy for MUSE-DWEPI with RPG in the head and neck region with a higher correlation (R2 = 0.791) compared with that for SS-DWEPI (R2 = 0.707) and MUSE-DWEPI (R2 = 0.745). MUSE-DWEPI with RPG significantly reduces the distortion compared with MUSE-DWEPI or conventional SS-DWEPI techniques, and the ADC values were similar.

The present study aims to monitor longitudinal changes in simulated tumor interstitial fluid pressure (IFP) and velocity (IFV) values using dynamic contrast-enhanced (DCE)-MRI-based computational fluid modeling (CFM) in pancreatic ductal adenocarcinoma (PDAC) patients. Nine PDAC patients underwent MRI, including DCE-MRI, on a 3-Tesla MRI scanner at pre-treatment (TX (0)), after the first fraction of stereotactic body radiotherapy (SBRT, (D1-TX)), and six weeks post-TX (D2-TX). The partial differential equation of IFP formulated from the continuity equation, incorporating the Starling Principle of fluid exchange, Darcy velocity, and volume transfer constant (Ktrans), was solved in COMSOL Multiphysics software to generate IFP and IFV maps. Tumor volume (Vt), Ktrans, IFP, and IFV values were compared (Wilcoxon and Spearman) between the time- points. D2-TX Ktrans values were significantly different from pre-TX and D1-TX (p &lt, 0.05). The D1-TX and pre-TX mean IFV values exhibited a borderline significant difference (p = 0.08). The IFP values varying &lt, 3.0% between the three time-points were not significantly different (p &gt, 0.05). Vt and IFP values were strongly positively correlated at pre-TX (r = 0.90, p = 0.005), while IFV exhibited a strong negative correlation at D1-TX (r = −0.74, p = 0.045). Vt, Ktrans, IFP, and IFV hold promise as imaging biomarkers of early response to therapy in PDAC.

The present study aimed to investigate the correlation at pre-treatment (TX) between quantitative metrics derived from multimodality imaging (MMI), including 18F-FDG-PET/CT, 18F-FMISO-PET/CT, DW- and DCE-MRI, using a community detection algorithm (CDA) in head and neck squamous cell carcinoma (HNSCC) patients. Twenty-three HNSCC patients with 27 metastatic lymph nodes underwent a total of 69 MMI exams at pre-TX. Correlations among quantitative metrics derived from FDG-PET/CT (SUL), FMSIO-PET/CT (K1, k3, TBR, and DV), DW-MRI (ADC, IVIM [D, D*, and f]), and FXR DCE-MRI [Ktrans, ve, and τi]) were investigated using the CDA based on a “spin-glass model” coupled with the Spearman’s rank, ρ, analysis. Mean MRI T2 weighted tumor volumes and SULmean values were moderately positively correlated (ρ = 0.48, p = 0.01). ADC and D exhibited a moderate negative correlation with SULmean (ρ ≤ −0.42, p &lt, 0.03 for both). K1 and Ktrans were positively correlated (ρ = 0.48, p = 0.01). In contrast, Ktrans and k3max were negatively correlated (ρ = −0.41, p = 0.03). CDA revealed four communities for 16 metrics interconnected with 33 edges in the network. DV, Ktrans, and K1 had 8, 7, and 6 edges in the network, respectively. After validation in a larger population, the CDA approach may aid in identifying useful biomarkers for developing individual patient care in HNSCC.

Current state-of-the-art models for estimating the pharmacokinetic parameters do not account for intervoxel movement of the contrast agent (CA). We introduce an optimal mass transport (OMT) formulation that naturally handles intervoxel CA movement and distinguishes between advective and diffusive flows. Ten patients with head and neck squamous cell carcinoma (HNSCC) were enrolled in the study between June 2014 and October 2015 and under-went DCE MRI imaging prior to beginning treatment. The CA tissue concentration information was taken as the input in the data-driven OMT model. The OMT approach was tested on HNSCC DCE data that provides quantitative information for forward flux (ΦF) and backward flux (ΦB). OMT-derived ΦF was compared with the volume transfer constant for CA, Ktrans, derived from the Extended Tofts Model (ETM). The OMT-derived flows showed a consistent jump in the CA diffusive behavior across the images in accordance with the known CA dynamics. The mean forward flux was 0.0082 ± 0.0091 (min-1) whereas the mean advective component was 0.0052±0.0086 (min-1) in the HNSCC patients. The diffusive percentages in forward and backward flux ranged from 8.67–18.76% and 12.76–30.36%, respectively. The OMT model accounts for intervoxel CA movement and results show that the forward flux (ΦF) is comparable with the ETM-derived Ktrans. This is a novel data-driven study based on optimal mass transport principles applied to patient DCE imaging to analyze CA flow in HNSCC.

Quantitative kurtosis phantoms are sought by multicenter clinical trials to establish accuracy and precision of quantitative imaging biomarkers on the basis of diffusion kurtosis imaging (DKI) parameters. We designed and evaluated precision, reproducibility, and long-term stability of a novel isotropic (i) DKI phantom fabricated using four families of chemicals based on vesicular and lamellar mesophases of liquid crystal materials. The constructed iDKI phantoms included negative control monoexponential diffusion materials to independently characterize noise and model-induced bias in quantitative kurtosis parameters. Ten test–retest DKI studies were performed on four scanners at three imaging centers over a six-month period. The tested prototype phantoms exhibited physiologically relevant apparent diffusion, Dapp, and kurtosis, Kapp, parameters ranging between 0.4 and 1.1 (×10−3 mm2/s) and 0.8 and 1.7 (unitless), respectively. Measured kurtosis phantom Kapp exceeded maximum fit model bias (0.1) detected for negative control (zero kurtosis) materials. The material-specific parameter precision [95% CI for Dapp: 0.013–0.022(×10−3 mm2/s) and for Kapp: 0.009–0.076] derived from the test–retest analysis was sufficient to characterize thermal and temporal stability of the prototype DKI phantom through correlation analysis of inter-scan variability. The present study confirms a promising chemical design for stable quantitative DKI phantom based on vesicular mesophase of liquid crystal materials. Improvements to phantom preparation and temperature monitoring procedures have potential to enhance precision and reproducibility for future multicenter iDKI phantom studies.

To develop and optimize a rapid magnetic resonance imaging (MRI) screening protocol for pancreatic cancer to be performed in conjunction with breast MRI screening in breast cancer susceptibility gene (BRCA)–positive individuals. An IRB-approved prospective study was conducted. The rapid screening pancreatic MR protocol was designed to be less than 10 min to be performed after a standard breast MRI protocol. Protocol consisted of coronal NT T2 SSFSE, axial NT T2 SSFSE and axial NT rFOV FOCUS DWI, and axial T1. Images were acquired with the patient in the same prone position of breast MRI using the built-in body coil. Image quality was qualitatively assessed by two radiologists with 12 and 13 years of MRI experience, respectively. The imaging protocol was modified until an endpoint of five consecutive patients with high-quality diagnostic images were achieved. Signal-to-noise ratio and contrast-to-noise ratio were assessed. The rapid pancreas MR protocol was successfully completed in all patients. Diagnostic image quality was achieved for all patients. Excellent image quality was achieved for low b values; however, image quality at higher b values was more variable. In one patient, a pancreatic neuroendocrine tumor was found and the patient was treated surgically. In four patients, small pancreatic cystic lesions were detected. In one subject, a hepatic mass was identified and confirmed as adenoma by liver MRI. Rapid MR protocol for pancreatic cancer screening is feasible and has the potential to play a role in screening BRCA patients undergoing breast MRI. • Develop and optimize a rapid magnetic resonance imaging (MRI) screening protocol for pancreatic cancer to be performed in conjunction with breast MRI screening in BRCA mutation positive individuals.

The aim of this study was to establish the repeatability measures of quantitative Gaussian and non-Gaussian diffusion metrics using diffusion-weighted imaging (DWI) data from phantoms and patients with head-and-neck and papillary thyroid cancers. The Quantitative Imaging Biomarker Alliance (QIBA) DWI phantom and a novel isotropic diffusion kurtosis imaging phantom were scanned at 3 different sites, on 1.5T and 3T magnetic resonance imaging systems, using standardized multiple b-value DWI acquisition protocol. In the clinical component of this study, a total of 60 multiple b-value DWI data sets were analyzed for test–retest, obtained from 14 patients (9 head-and-neck squamous cell carcinoma and 5 papillary thyroid cancers). Repeatability of quantitative DWI measurements was assessed by within-subject coefficient of variation (wCV%) and Bland–Altman analysis. In isotropic diffusion kurtosis imaging phantom vial with 2% ceteryl alcohol and behentrimonium chloride solution, the mean apparent diffusion (Dapp × 10−3 mm2/s) and kurtosis (Kapp, unitless) coefficient values were 1.02 and 1.68 respectively, capturing in vivo tumor cellularity and tissue microstructure. For the same vial, Dapp and Kapp mean wCVs (%) were ≤1.41% and ≤0.43% for 1.5T and 3T across 3 sites. For pretreatment head-and-neck squamous cell carcinoma, apparent diffusion coefficient, D, D*, K, and f mean wCVs (%) were 2.38%, 3.55%, 3.88%, 8.0%, and 9.92%, respectively, wCVs exhibited a higher trend for papillary thyroid cancers. Knowledge of technical precision and bias of quantitative imaging metrics enables investigators to properly design and power clinical trials and better discern between measurement variability versus biological change.

The aim of the present study was to identify whether the quantitative metrics from pre-treatment (TX) non-Gaussian intravoxel incoherent motion (NGIVIM) diffusion weighted (DW-) and fast exchange regime (FXR) dynamic contrast enhanced (DCE)-MRI can predict patients with locoregional failure (LRF) in nasopharyngeal carcinoma (NPC). Twenty-nine NPC patients underwent pre-TX DW- and DCE-MRI on a 3T MR scanner. DW imaging data from primary tumors were fitted to monoexponential (ADC) and NGIVIM (D, D*, f, and K) models. The metrics Ktrans, ve, and τi were estimated using the FXR model. Cumulative incidence (CI) analysis and Fine-Gray (FG) modeling were performed considering death as a competing risk. Mean ve values were significantly different between patients with and without LRF (p = 0.03). Mean f values showed a trend towards the difference between the groups (p = 0.08). Histograms exhibited inter primary tumor heterogeneity. The CI curves showed significant differences for the dichotomized cutoff value of ADC ≤ 0.68 × 10−3 (mm2/s), D ≤ 0.74 × 10−3 (mm2/s), and f ≤ 0.18 (p &lt, 0.05). τi ≤ 0.89 (s) cutoff value showed borderline significance (p = 0.098). FG’s modeling showed a significant difference for the K cutoff value of ≤0.86 (p = 0.034). Results suggest that the role of pre-TX NGIVIM DW- and FXR DCE-MRI-derived metrics for predicting LRF in NPC than alone.

Youth fishing programs are an important gateway into continued fishing participation. With the current focus on R3 (recruitment, retention, and reactivation), it is important to understand the impacts fishing programs can have on their participants' knowledge, confidence, and interest in continuation. In this study, we conducted retrospective pre-post surveys of participants in a high school fishing program in Florida, USA, and compared results to a group of non-participating peers. We found significant increases in knowledge and confidence related to fishing skills among participants and significantly higher skills and confidence reported by participants as compared to non-participants. We also saw higher levels of self-identity as an angler as well as more desire to continue fishing on their own as compared to non-participants. The positive impacts of programs like this are important to the recruitment and retention of young anglers and continued evaluation of their effectiveness will lead to improved outreach programming.

Pharmacologically induced hypothermia (PIH) shows promising neuroprotective effects after stroke insult. However, the dynamic evolution of stroke infarct during the hypothermic therapy has not been understood very well. In the present study, MRI was utilized to longitudinally characterize the infarct evolution in a mouse model of ischemic stroke treated by PIH using the neurotensin agonist HPI201. Adult male C57BL/6 mice underwent permanent occlusion of the right middle cerebra artery (MCA). Each animal received a vehicle or HPI201 intraperitoneal injection. The temporal changes of stroke lesion were examined using T2-weighted imaging and diffusion-weighted imaging (DWI) in the acute phase (1 − 3h) and 24 h post stroke. Significantly reduced infarct and edema volumes were observed in PIH treated stroke mice, in agreement with TTC staining findings. Also, the TUNEL staining results indicated apoptotic cells were widely distributed among the ischemic cortex in control group but limited in PIH treated mice. Dramatically reduced growth rate of infarction was seen in PIH treated stroke mice. These results demonstrate HPI201 has strong neuroprotection effects during acute stroke. In particular, MRI with the numerical modelling of temporal infarct evolution could provide a unique means to examine and predict the dynamic response of the PIH treatment on infarct evolution.

AIM To noninvasively investigate tumor cellularity measured using diffusion-weighted magnetic resonance imaging (DW-MRI) and glucose metabolism measured by 18F-labeled fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) during radiation therapy (RT) for human papillomavirus negative (HPV-) head and neck squamous cell carcinoma (HNSCC). METHODS In this prospective study, 6 HPV- HNSCC patients underwent a total of 34 multimodality imaging examinations DW-MRI at 1.5 T Philips MRI scanner [(n = 24) pre-, during- (2-3 wk), and post-treatment (Tx), and 18F-FDG PET/CT pre- and post-Tx (n = 10)]. All patients received RT. Monoexponential modeling of the DW-MRI data yielded the imaging metric apparent diffusion coefficient (ADC) and the mean of standardized uptake value (SUV) was measured from 18F-FDG PET uptake. All patients had a clinical follow-up as the standard of care and survival status was documented at 1 year. RESULTS There was a strong negative correlation between the mean of pretreatment ADC (ρ = -0.67, P = 0.01) and the pretreatment 18F-FDG PET SUV. The percentage (%) change in delta (∆) ADC for primary tumors and neck nodal metastases between pre- and Wk2-3 Tx were as follows: 75.4% and 61.6%, respectively, for the patient with no evidence of disease, 27.5% and 32.7%, respectively, for those patients who were alive with disease, and 26.9% and 7.31%, respectively, for those who were dead with disease. CONCLUSION These results are preliminary in nature and are indicative, and not definitive, trends rendered by the imaging metrics due to the small sample size of HPV- HNSCC patients in a Meixoeiro Hospital of Vigo Experience.

We assessed a priori aggressive features using quantitative diffusion-weighted imaging metrics to preclude an active surveillance management approach in patients with papillary thyroid cancer (PTC) with tumor size 1–2 cm. This prospective study enrolled 24 patients with PTC who underwent pretreatment multi-b-value diffusion-weighted imaging on a GE 3 T magnetic resonance imaging scanner. The apparent diffusion coefficient (ADC) metric was calculated from monoexponential model, and the perfusion fraction (f), diffusion coefficient (D), pseudo-diffusion coefficient (D*), and diffusion kurtosis coefficient (K) metrics were estimated using the non-Gaussian intravoxel incoherent motion model. Neck ultrasonography examination data were used to calculate tumor size. The receiver operating characteristic curve assessed the discriminative specificity, sensitivity, and accuracy between PTCs with and without features of tumor aggressiveness. Multivariate logistic regression analysis was performed on metrics using a leave-1-out cross-validation method. Tumor aggressiveness was defined by surgical histopathology. Tumors with aggressive features had significantly lower ADC and D values than tumors without tumor-aggressive features (P &lt, 05). The absolute relative change was 46% in K metric value between the 2 tumor types. In total, 14 patients were in the critical size range (1–2 cm) measured by ultrasonography, and the ADC and D were significantly different and able to differentiate between the 2 tumor types (P &lt, 05). ADC and D can distinguish tumors with aggressive histological features to preclude an active surveillance management approach in patients with PTC with tumors measuring 1–2 cm.

Stroke is a devastating neurovascular disorder that results in damage to neurons and white matter tracts. It has been previously demonstrated that neuregulin-1 (NRG-1) protects neurons from ischemic injury following stroke. Here, diffusion tensor imaging (DTI) was utilized to characterize the effects of NRG-1 treatment on cererbral infarction and integrity of white matter after ischemic insult using a permanent middle celebral artery occlusion (pMCAo) rat model. In the present study, sixteen Sprague-Dawley rats underwent pMCAo surgery and received either a single intra-arterial bolus (20 μg/kg) dose of NRG-1 or saline immediately prior to pMCAo. MRI including T2-weighted imaging and DTI was performed in the first 3 h post stroke, and repeated 48 h later. It is found that the stroke infarction was significantly reduced in the NRG-1 treated group. Also, NRG-1 prevented the reduction of fractional anisotropy (FA) in white matter tracts of fornix and corpus callosum (CC), indicating its protection of CC and fornix white matter bundles from ischemia insult. As a conclusion, the present DTI results demonstrate that NRG-1 has significantly neuroprotective effects in both cerebral cortex and white matter including corpus callosum and fornix during acute stroke. In particular, NRG-1 is more effective on stroke lesion with mild ischemia. As CC and fornix white matter bundles play critical roles in transcallosal connectivity and hippocampal projections respectively in the central nervous system, the findings could provide complementary information for better understanding the biological mechanism of NRG-1's neuroprotection in ischemic tissues and neurobehavioral effects.

The purpose of this study was to identify the optimal tracer kinetic model from dynamic contrast-enhanced T(1)‐weighted magnetic resonance imaging (DCE-MRI) data and evaluate whether parameters estimated from the optimal model predict tumor aggressiveness determined from histopathology in patients with papillary thyroid carcinoma (PTC) prior to surgery. In this prospective study, 18 PTC patients underwent pretreatment DCE-MRI on a 3T MR scanner prior to thyroidectomy. This study was approved by the institutional review board and informed consent was obtained from all patients. The two-compartment exchange model (2CXM), compartmental tissue uptake model (CTUM), extended Tofts model (ETM), and standard Tofts model (TM) were compared on a voxel-wise basis to determine the optimal model using the corrected Akaike information criterion (AICc) for PTC. The optimal model is the one with the lowest AICc. Statistical analysis included paired and unpaired t-tests and a one-way Analysis of variance. Bonferroni correction was applied for multiple comparisons. Receiver operating characteristic (ROC) curves were generated from the optimal model parameters to differentiate PTC with and without aggressive features, and AUC’s were compared. ETM performed the best with the lowest AICc and highest weights (0.44) among the four models. ETM was preferred in 44% of all 3419 voxels. The ETM estimates of K(trans) in PTCs with aggressive feature extrathyroidal extension (ETE) were significantly higher than those without ETE (0.78±0.29 vs. 0.34±0.18 min(−1), P=0.005). From ROC analysis, cut-off values of K(trans), v(e), and v(p) which discriminated between PTCs with and without ETE were determined at 0.45 min(−1), 0.28, and 0.014, respectively. The sensitivities and specificities were 86% and 82% (K(trans)), 71% and 82% (v(e)), and 86% and 55% (v(p)). Their respective AUC’s were 0.90, 0.71, and 0.71. We conclude the ETM K(trans) has shown potential to classify tumors with and without aggressive ETE in patients with PTC.

Prescribed burning and other active forest management treatments have been proven essential for maintaining suitable habitat conditions for many wildlife species, including the federally endangered red-cockaded woodpecker (RCW). This study examines the perception of forest management treatments of recreation users participating in various activities (hunting, hiking/backpacking, camping, off-highway vehicle riding, and canoeing/kayaking) in terms of scenic beauty and recreation satisfaction. We used photographic images to capture various forest management treatments of different intensity levels and times after treatments, and assessed users’ perception of scenic beauty and recreation satisfaction. Results indicated variation among users participating in different recreation activities, but that good quality RCW habitats offered both higher scenic beauty and higher recreation satisfaction than poor quality habitats for most activity user groups. Finally, recreation satisfaction was statistically equal to perceived scenic beauty from both good and poor-quality RCW habitats for most of the activity user groups, thus suggesting the importance of scenic beauty of forest sites in determining recreation users’ attainment of visit satisfaction. Findings conclude that forest sites developed as good quality RCW habitats in the present state also offer quality experience to recreation users, thus supporting multi-objective forestry practices in public forests.

This study examines effects of weather, temporal factors, and gasoline price on outdoor recreation participation by using a time series model. We obtained more than 5 years of daily outdoor recreation visitation data by using infrared mechanical counters on a section of the Florida National Scenic Trail (FNST). Results showed that days with daily maximum temperatures of 16–22 °C brought the largest number of visitors, which suggests this is the most comfortable range of daily maximum temperatures to recreate on the FNST. Daily maximum temperatures below 6 °C and above 31 °C and heat index values above 38 °C brought significantly lower visitor numbers, suggesting these values are temperature thresholds for this region in a recreation context. A seasonal autoregressive integrated moving average model showed significant negative effects of temperature, relative humidity, cold snaps, and gasoline price and a positive effect of weekends and public holidays on recreational visitations to this trail. Days with heavy rainfall (> 2.54 cm) or a high heat index (≥ 35 °C) were likely to negatively affect recreation participation not only on the same day, but also on the next normal weather day. These findings imply that managers of facilities that need staffing and other resources should expect to receive fewer visitors on days following adverse weather conditions, even if that day has normal weather conditions.

Purpose: The ability to longitudinally monitor cell grafts and assess their condition is critical for the clinical translation of stem cell therapy in regenerative medicine. Developing an inducible genetic magnetic resonance imaging (MRI) reporter will enable non-invasive and longitudinal monitoring of stem cell grafts in vivo. Methods: MagA, a bacterial gene involved in the formation of iron oxide nanocrystals, was genetically modified for in vivo monitoring of cell grafts by MRI. Inducible expression of MagA was regulated by a Tet-On (Tet) switch. A mouse embryonic stem cell-line carrying Tet-MagA (mESC-MagA) was established by lentivirus transduction. The impact of expressing MagA in mESCs was evaluated via proliferation assay, cytotoxicity assay, teratoma formation, MRI, and inductively coupled plasma atomic emission spectroscopy (ICP-OES). Mice were grafted with mESCs with and without MagA (mESC-MagA and mESC-WT). The condition of cell grafts with induced “ON” and non-induced “OFF” expression of MagA was longitudinally monitored in vivo using a 7T MRI scanner. After imaging, whole brain samples were harvested for histological assessment. Results: Expression of MagA in mESCs resulted in significant changes in the transverse relaxation rate (R2 or 1/T2) and susceptibility weighted MRI contrast. The pluripotency of mESCs carrying MagA was not affected in vitro or in vivo. Intracranial mESC-MagA grafts generated sufficient T2 and susceptibility weighted contrast at 7T. The mESC-MagA grafts can be monitored by MRI longitudinally upon induced expression of MagA by administering doxycycline (Dox) via diet. Conclusion: Our results demonstrate MagA could be used to monitor cell grafts noninvasively, longitudinally, and repetitively, enabling the assessment of cell graft conditions in vivo.

Purpose Characterize and monitor treatment response in human papillomavirus (HPV) head and neck squamous cell carcinoma (HNSCC) using intra‐treatment (intra‐TX) imaging metrics derived from intravoxel incoherent motion (IVIM) diffusion‐weighted magnetic resonance imaging (DW‐MRI). Materials and Methods Thirty‐four (30 HPV positive [+] and 4 HPV negative [‐]) HNSCC patients underwent a total of 136 MRI including multi‐b value DW‐MRI (pretreatment [pre‐TX] and intra‐TX weeks 1, 2, and 3) at 3.0 Tesla. All patients were treated with chemo‐radiation therapy. Monoexponential (yielding apparent diffusion coefficient [ADC]) and bi‐exponential (yielding perfusion fraction [f], diffusion [D], and pseudo‐diffusion [D*] coefficients) fits were performed on a region of interest and voxel‐by‐voxel basis, on metastatic neck nodes. Response was assessed using RECISTv1.1. The relative percentage change in D, f, and D* between the pre‐ and intra‐TX weeks were used for hierarchical clustering. A Wilcoxon rank‐sum test was performed to assess the difference in metrics within and between the complete response (CR) and non‐CR groups. Results The delta (Δ) change in volume (V)1wk‐0wk for the CR group differed significantly (P = 0.016) from the non‐CR group, while not for V2wk‐0wk and V3wk‐0wk (P > 0.05). The mean increase in ΔD3wk‐0wk for the CR group was significantly higher (P = 0.017) than the non‐CR group. ADC and D showed an increasing trend at each intra‐TX week when compared with pre‐TX in CR group (P

This paper models the behavior of the longitudinal relaxation rate of the protons of tissue water R1 (R1 = 1/T1), measured in a Look-Locker experiment at 7 Tesla after administration of a paramagnetic contrast agent (CA). It solves the Bloch-McConnell equations for the longitudinal magnetization of the protons of water in a three-site two-exchange (3S2X) model with boundary conditions appropriate to repeated sampling of magnetization. The extent to which equilibrium intercompartmental water exchange kinetics affect monoexponential estimates of R1 after administration of a CA in dynamic contrast enhanced experiment is described. The relation between R1 and tissue CA concentration was calculated for CA restricted to the intravascular, or to the intravascular and extracellular compartments, by varying model parameters to mimic experimental data acquired in a rat model of cerebral tumor. The model described a nearly linear relationship between R1 and tissue concentration of CA, but demonstrated that the apparent longitudinal relaxivity of CA depends upon tissue type. The practical consequence of this finding is that the extended Patlak plot linearizes the ΔR1 data in tissue with leaky microvessels, accurately determines the influx rate of the CA across these microvessels, but underestimates the volume of intravascular blood water. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.

The apparent forward transfer constant, K transa, for albumin was measured in 9L cerebral tumors in 15 rats. An MRI study using gadolinium-labeled bovine serum albumin was followed by terminal quantitative autoradiography (QAR) using radioiodinated serum albumin. Look-Locker MRI estimates of T(1) followed gadolinium-labeled bovine serum albumin blood and tissue concentration. QAR and MRI maps of K transa were coregistered, a region of interest (ROI) that included the tumor and its surround was selected, and the two estimates of K transa from the ROI on QAR and MRI maps were compared by either mean per animal ROI or on pixel-by-pixel data using a generalized estimating equation. An ROI analysis showed a moderate correlation between the two measures (r = 0.57, P = 0.026); pixel-by-pixel generalized estimating equation analysis concurred (r = 0.54, P < 0.0001). The estimates of QAR with MRI of last time points (e.g., 25 min) showed a moderate correlation (ROI r = 0.55, P < 0.035; generalized estimating equation r = 0.58, P < 0.0001). Differences between the QAR and MRI estimates of K transa did not differ from zero, but the MRI 25-min estimate was significantly lower than the QAR estimate. Thus, noninvasive MRI estimates of vascular permeability can serve as a surrogate for QAR measures.

Information about the factors associated with conservation participation by local communities is important to garner support and involvement within a natural protected area. This research examined how residents&rsquo, natural resource dependency and other social, economic, and access-related variables predict conservation participation. Data were collected based on a stratified random sampling of households from Gaurishankar Conservation Area Project (GCAP)&mdash, a newly designated mountainous protected area in Nepal. Analysis was conducted via an ordered logistic regression model. Higher levels of participation were observed among households that comprised of a larger family size, belonged to a higher caste/ethnicity, resided in higher elevations, and noted frequent visits and interactions with park management staff. However, natural resources dependency (i.e., income and fuelwood fodder) lacked a statistically significant relationship with conservation participation. Similarly, the economic dimension (i.e., land holdings and total livestock unit) was not a significant predictor of participation. Overall, key findings suggest that conservation participation at GCAP needs to be improved with multiple outreach activities, especially to resource-dependent households. More specifically, it is important to ensure equitable access so that locals can participate in programs that provide alternative resource use options, skills development, and trainings for income generation activities.

THE PURPOSE OF THIS STUDY was to develop an MRI technique for evaluating acute drug action (i.e., within one to two hours of administration) upon blood-brain exchange in an experimental cerebral tumor. To accomplish this, a standard cerebral tumor model, the 9L gliosarcoma in Fischer 344 rats (1,2), was employed, and the blood-brain distribution of the macromolecular magnetic resonance contrast agent (MRCA), Gadomer, was assessed quantitatively by MRI both before (test data) and shortly after (retest data) drug administration. Of importance in the selection of this MRCA and the development of this technique, Gadomer is relatively rapidly cleared from the blood (half-life ≈ 30 minutes (3)). To produce an in vivo change in the blood-brain distribution system and test the sensitivity in time of this MRI procedure, dexamethasone was administered to the experimental animals after test data acquisition. Postprocessing analyses yielded sets of blood-brain transfer constants—flux rates and distribution spaces—appropriate to one of three models (4). The test-retest differences in the four transfer constants were calculated and used for statistical analysis of drug effects. As to the choice of drug, the effects of dexamethasone on blood-brain tumor exchange of radioiodinated serum albumin (RISA) has been previously imaged by quantitative autoradiography of a different rat cerebral tumor model, the RG2 glioma (5): The effect of dexamethasone on tumor vascular permeability in another brain tumor model has been previously studied using RISA (5): in that experiment, dexamethasone lowered the transvascular transfer constant and the extravascular distribution space of RISA in the RG2 glioma model, but did not produce a significant change in the tumor plasma volume. Therefore, it was assumed that dexamethasone would have similar effects on the blood-brain distribution of Gadomer in the rat 9L model and this combination of MRCA and tumor would serve as a good proving ground of the test-retest MRI technique for assessing acute drug action.

The neuroprotective effects of neuregulin-1 (NRG-1) on stroke lesions were assessed longitudinally in rats with middle cerebral artery occlusion (MCAo) using MRI. Sprague-Dawley rats (n=16, 250±20g) underwent permanent MCAo surgery with cerebral blood flow (CBF) monitored by laser doppler flowmetry at ipsilateral side of bregma for 20 minutes post occlusion. A single 50 μl bolus dose of NRG-1 or vehicle was administered into the left internal carotid artery immediately prior to MCAo. The expansion of the ischemic lesion into the cortex was attenuated by NRG-1 over a 48-hour(hr) time span as measured by diffusion weighted imaging (DWI). The final infarct volumes of NRG-1 treated rats were significantly smaller than those of the vehicle treated group at 48 hr (264.8 ± 192.1 vs. 533.4 ± 175.5 mm(3), p70% CBF reduction). In particular, ischemic infarction was not usually observed in the cortex of NRG-1 treated rats with mild ischemia at 3 and 48 hr post occlusion. Histological results validated the imaging findings and demonstrated that NRG-1 treated rats had fewer injured neurons in peri-infarct areas 48 hr post ischemia. In summary, the longitudinal neuroprotective effect of NRG-1 in the pMCAo stroke model was demonstrated by prevention of ischemic lesion expansion, reduced infarct volume and protection of neurons from ischemic damage.

Classical descriptions of tumor physiology suggest two origins for tumor hypoxia; steady-state (diffusion-limited) hypoxia and cycling (perfusion-modulated) hypoxia. Both origins, primarily studied and characterized in murine models, predict relatively small, isolated foci or thin shells of hypoxic tissue interspersed with contrasting oxic tissue. These foci or shells would not be expected to scale with overall tumor size since the oxygen diffusion distance (determined by oxygen permeability and tissue oxygen consumption rate) is not known to vary dramatically from tumor to tumor. We have identified much larger (macroscopic) regions of hypoxia in rat gliosarcoma tumors and in larger human tumors (notably sarcomas and high-grade glial tumors), as indicated by biochemical binding of the hypoxia marker, EF5. Thus, we considered an alternative cause of tumor hypoxia related to a phenomenon first observed in window-chamber tumor models: namely longitudinal arteriole gradients. Although longitudinal arteriole gradients, as originally described, are also microscopic in nature, it is possible for them to scale with tumor size if tumor blood flow is organized in an appropriate manner. In this organization, inflowing blood would arise from relatively well-oxygenated sources and would branch and then coalesce to poorly-oxygenated outflowing blood over distances much larger than the length of conventional arterioles (multi-millimeter scale). This novel concept differs from the common characterization of tumor blood flow as disorganized and/or chaotic. The organization of blood flow to produce extended longitudinal gradients and macroscopic regional hypoxia has many important implications for the imaging, therapy and biological properties of tumors. Herein, we report the first experimental evidence for such blood flow, using rat 9L gliosarcoma tumors grown on the epigastric artery/vein pair.

Dynamic contrast enhanced T(1)-weighted MRI using the contrast agent gadopentetate dimeglumine (Gd-DTPA) was performed on 10 patients with glioblastoma. Nested models with as many as three parameters were used to estimate plasma volume or plasma volume and forward vascular transfer constant (K(trans)) and the reverse vascular transfer constant (k(ep)). These constituted models 1, 2, and 3, respectively. Model 1 predominated in normal nonleaky brain tissue, showing little or no leakage of contrast agent. Model 3 predominated in regions associated with aggressive portions of the tumor, and model 2 bordered model 3 regions, showing leakage at reduced rates. In the patient sample, v(p) was about four times that of white matter in the enhancing part of the tumor. K(trans) varied by a factor of 10 between the model 2 (1.9 ↔ 10(-3) min(-1)) and model 3 regions (1.9 ↔ 10(-2) min(-1)). The mean calculated interstitial space (model 3) was 5.5%. In model 3 regions, excellent curve fits were obtained to summarize concentration-time data (mean R(2) = 0.99). We conclude that the three parameters of the standard model are sufficient to fit dynamic contrast enhanced T(1) data in glioblastoma under the conditions of the experiment.

The longitudinal relaxivity on the protons of water of a Gd–chelate–albumin compound was measured at 7 T as a function of the macromolecular content of a cross-linked matrix. In agreement with previous works, the results demonstrate that the effect of gadolinium on water proton relaxivity is not constant, rising moderately with increase in the concentration of bovine serum albumin (BSA). About 35% variation in relaxivity was observed over a 0%–25% range of BSA concentrations (ℜ = 3.893 + 0.0502 × BSA [%], SE = 0.0119 and 0.1740, t = 4.215 and 22.383, p