First-in-Human Hyperpolarized MRI for Tumor Metabolism in HNSCC.

This case report describes the use of hyperpolarized magnetic resonance imaging (MRI) in a patient with head and neck squamous cell carcinoma (HNSCC) to demonstrate its translational viability.

Mutual-information based optimal experimental design for hyperpolarized [Formula: see text]C-pyruvate MRI.

A key parameter of interest recovered from hyperpolarized (HP) MRI measurements is the apparent pyruvate-to-lactate exchange rate, [Formula: see text], for measuring tumor metabolism. This manuscript presents an information-theory-based optimal experimental design approach that minimizes the uncertainty in the rate parameter, [Formula: see text], recovered from HP-MRI measurements. Mutual information is employed to measure the information content of the HP measurements with respect to the first-order exchange kinetics of the pyruvate conversion to lactate. Flip angles of the pulse sequence acquisition are optimized with respect to the mutual information. A time-varying flip angle scheme leads to a higher parameter optimization that can further improve the quantitative value of mutual information over a constant flip angle scheme. However, the constant flip angle scheme, 35 and 28 degrees for pyruvate and lactate measurements, leads to an accuracy and precision comparable to the variable flip angle schemes obtained from our method. Combining the comparable performance and practical implementation, optimized pyruvate and lactate flip angles of 35 and 28 degrees, respectively, are recommended.

Distinguishing Intrathyroid Parathyroid Adenoma from Colloid Nodules and Papillary Thyroid Carcinomas Using Multiphasic Multidetector Computed Tomography.

OBJECTIVE: The aim of the study is to determine whether multiphase multidetector computed tomography (4D-MDCT) can differentiate between intrathyroid parathyroid adenomas (ITPAs), colloid nodules, and papillary thyroid carcinoma (PTC). METHODS: We studied 22 ITPAs, 22 colloid nodules, and 11 PTCs in 55 patients. Hounsfield unit (HU) values of the nodules were measured on 4D-MDCT in the precontrast, arterial, venous, and delayed phases. Raw HU values, phase with peak enhancement, and washout percentages between the phases were evaluated. RESULTS: Regardless of size, all ITPAs (22/22) showed peak enhancement in the arterial phase, which was significantly greater than both colloid nodules (15/22) and PTC (6/11, P = 0.002); thus, nodules with peak enhancement in the venous or delayed phase were not ITPAs (specificity = 1). For nodules with peak enhancement in the arterial phase, the percentage washout in the arterial-to-venous phases separated ITPAs from PTC and colloid nodules (P < 0.001) with greater than or equal to 23.95% loss of HU value implying IPTA (area under curve, 0.79). This left a subset of colloid nodules or PTC that either peaked in the venous or delayed phase or had an arterial-to-venous phase washout of less than 23.95%. From this subset, PTC measuring 1 cm or greater could be separated from colloid based on HU values in the arterial phase with a cutoff HU value less than 81.4 for PTC (area under curve, 0.72) and an HU value greater than 164.5 suggested colloid. CONCLUSIONS: Intrathyroid parathyroid adenomas can be distinguished from colloid nodules and PTC by peak enhancement in the arterial phase and rapid washout. A subset of colloid and PTC measuring 1 cm or greater can be separated using arterial phase HU values.

An efficient magnetic resonance image data quality screening dashboard.

PURPOSE: Complex data processing and curation for artificial intelligence applications rely on high-quality data sets for training and analysis. Manually reviewing images and their associated annotations is a very laborious task and existing quality control tools for data review are generally limited to raw images only. The purpose of this work was to develop an imaging informatics dashboard for the easy and fast review of processed magnetic resonance (MR) imaging data sets; we demonstrated its ability in a large-scale data review. METHODS: We developed a custom R Shiny dashboard that displays key static snapshots of each imaging study and its annotations. A graphical interface allows the structured entry of review data and download of tabulated review results. We evaluated the dashboard using two large data sets: 1380 processed MR imaging studies from our institution and 285 studies from the 2018 MICCAI Brain Tumor Segmentation Challenge (BraTS). RESULTS: Studies were reviewed at an average rate of 100/h using the dashboard, 10 times faster than using existing data viewers. For data from our institution, 1181 of the 1380 (86%) studies were of acceptable quality. The most commonly identified failure modes were tumor segmentation (9.6% of cases) and image registration (4.6% of cases). Tumor segmentation without visible errors on the dashboard had much better agreement with reference tumor volume measurements (root-mean-square error 12.2 cm3 ) than did segmentations with minor errors (20.5 cm3 ) or failed segmentations (27.4 cm3 ). In the BraTS data, 242 of 285 (85%) studies were acceptable quality after processing. Among the 43 cases that failed review, 14 had unacceptable raw image quality. CONCLUSION: Our dashboard provides a fast, effective tool for reviewing complex processed MR imaging data sets. It is freely available for download at https://github.com/EGates1/MRDQED.

Rate of incidental central nervous system meningioma detected in patients undergoing 18F-fluciclovine PET/CT imaging for evaluation of prostate cancer.

OBJECTIVE: To evaluate the rate of incidental detection of central nervous system (CNS) meningioma in patients undergoing 18F-fluciclovine PET/computed tomography (CT) imaging for the evaluation of prostate cancer. METHODS: The reports of 850 18F-fluciclovine PET/CT scans in 566 patients with pathologically proven prostate cancer performed from April 2017 to July 2019, were retrospectively reviewed for the presence of CNS meningioma. RESULTS: A total of 14 patients (2.8%) (age range: 54-82 years old) had abnormal focal intracranial 18F-fluciclovine uptake, all extra-axial in location (SUVmax range: 3.2-19.3). Two cases out of 14 (0.35%) were diagnosed as metastatic lesions. Twelve out of the 14 patients, had 18F-fluciclovine PET/CT imaging findings suspicious for CNS meningioma, 2 of them received another diagnosis on further imaging, and only 10 cases (2%) had the diagnosis of meningioma according to follow-up MRI and 18F-fluciclovine PET/CT. CONCLUSION: Focal 18F-fluciclovine avid intracranial lesions incidentally detected in patients undergoing PET/CT imaging for prostate cancer are most often CNS meningiomas.

Disease Characteristics, Radiologic Patterns, Comorbid Diseases, and Ethnic Differences in 32 Patients With Rosai-Dorfman Disease.

OBJECTIVE: Rosai-Dorfman disease (RDD) is a rare and idiopathic nonneoplastic disease of histiocytes that is characterized by lymphadenopathy and extranodal disease. In this study, we documented anatomical preferences, imaging findings, comorbid diseases, and ethnic differences in 32 RDD patients. METHODS: We conducted a retrospective review of pathologically confirmed cases seen at our institution from 1998 to 2016. These cases were analyzed for (a) anatomical locations, (b) radiologic appearance, (c) comorbid diseases, and (d) differences between ethnic groups. RESULTS: We found 32 patients with RDD, 18 were women and 14 were men. There were 51 lesions in all patients, 23.5% of which were nodal, involving 11 lymph node regions, and 76.5% were extranodal. Cervical lymph nodes and maxillofacial area were the most common affected nodal and extranodal locations, respectively. Only 4 (12.5%) of 32 patients had pure nodal involvement, whereas 20 (62.5%) of 32 had pure extranodal disease and 8 (25%) of 32 had mixed nodal and extranodal disease.Anatomically, RDD affected multiple organs in our cohort, including the lymphatic system, maxillofacial area (glandular and nonglandular tissues), superficial soft tissue, central nervous system, breast, peritoneum, gastrointestinal tract, and lungs.Radiologically, RDD presentation was variable from an organ to another. However, most lesions were hypermetabolic on 18F-fluorodeoxyglucose positron-emission tomography/computed tomography and isointense on T1-weighted magnetic resonance imaging. Computed tomographic findings were extremely variable between organs.Comorbid diseases were found in 11 patients. Those patients had 17 comorbid diseases; the most common were autoimmune diseases, viral diseases, and cancer.The organ distribution of RDD was slightly different between ethnic groups. The most frequent disease location for African Americans was lymph nodes; for whites, central nervous system and nonglandular maxillofacial (27.3% each); for Asians, lymph nodes, subcutaneous tissue, and nonglandular maxillofacial (25% each); and for Hispanics, lymph nodes and glandular maxillofacial (33.3% each). CONCLUSIONS: Rosai-Dorfman disease represents a wide-spectrum disease not limited to lymph nodes. Radiologically, RDD has diverse imaging findings. However, most lesions were hypermetabolic on 18F-fluorodeoxyglucose positron-emission tomography/computed tomography and isointense on T1-weighted imaging. Patients with RDD have a high rate of comorbid diseases including autoimmune disease, viral infections, and cancer.

Hyperpolarized Pyruvate MR Spectroscopy Depicts Glycolytic Inhibition in a Mouse Model of Glioma.

BackgroundA generation of therapies targeting tumor metabolism is becoming available for treating glioma. Hyperpolarized MRI is uniquely suited to directly measure the metabolic effects of these emerging treatments.PurposeTo explore the feasibility of the use of hyperpolarized [1-carbon 13 {13C}]-pyruvate for real-time measurement of metabolism and response to treatment with a glycolytic inhibitor in an orthotopic mouse model of glioma.Materials and MethodsIn this animal study, anatomic MRI and dynamic 13C MR spectroscopy were performed at 7 T during intravenous injection of hyperpolarized [1-13C]-pyruvate on mice with orthotopic U87MG glioma and healthy control mice. Anatomic MRI and dynamic 13C MR spectroscopy were repeated after administration of the glycolytic inhibitor WP1122, a prodrug of 2-deoxy-d-glucose. All experiments were conducted in athymic nude mice between October 2016 and March 2017. Hyperpolarized lactate production was quantified as an apparent reaction rate, or kPL, and normalized lactate ratio (nLac). The Wilcoxon signed-rank test was used to assess changes in paired measures of lactate production before and after treatment.ResultsThirteen 12-16-week-old female mice and five healthy female mice underwent anatomic MRI and hyperpolarized [1-13C]-pyruvate spectroscopy. Large contrast agent-enhanced tumors were shown in mice with glioma at T2-weighted and T1-weighted postcontrast MRI by postimplantation day 40. After treatment with WP1122, a decrease in lactate was observed in mice with glioma (baseline and treatment mean kPL, 0.027 and 0.018 sec-1, respectively, P = .01; baseline and posttreatment mean nLac, 0.28 and 0.22, respectively, P = .01) whereas no significant decrease was observed in healthy control mice (baseline and posttreatment mean kPL, 0.011 and 0.017 sec-1, respectively, P = .91; baseline and posttreatment mean nLac, 0.16 and 0.21, respectively, P = .84).ConclusionHyperpolarized carbon 13 measurements of pyruvate metabolism can provide rapid feedback for monitoring treatment response in glioma.© RSNA, 2019.

Spatial Distance Correlates With Genetic Distance in Diffuse Glioma.

Background: Treatment effectiveness and overall prognosis for glioma patients depend heavily on the genetic and epigenetic factors in each individual tumor. However, intra-tumoral genetic heterogeneity is known to exist and needs to be managed. Currently, evidence for genetic changes varying spatially within the tumor is qualitative, and quantitative data is lacking. We hypothesized that a greater genetic diversity or "genetic distance" would be observed for distinct tumor samples taken with larger physical distances between them. Methods: Stereotactic biopsies were obtained from untreated primary glioma patients as part of a clinical trial between 2011 and 2016, with at least one biopsy pair collected in each case. The physical (Euclidean) distance between biopsy sites was determined using coordinates from imaging studies. The tissue samples underwent whole exome DNA sequencing and epigenetic methylation profiling and genomic distances were defined in three separate ways derived from differences in number of genes, copy number variations (CNV), and methylation profiles. Results: Of the 31 patients recruited to the trial, 23 were included in DNA methylation analysis, for a total of 71 tissue samples (14 female, 9 male patients, age range 21-80). Samples from an 8 patient subset of the 23 evaluated patients were further included in whole exome and copy number variation analysis. Physical and genomic distances were found to be independently and positively correlated for each of the three genomic distance measures. The correlation coefficients were 0.63, 0.65, and 0.35, respectively for (a) gene level mutations, (b) copy number variation, and (c) methylation status. We also derived quantitative linear relationships between physical and genomic distances. Conclusion: Primary brain tumors are genetically heterogeneous, and the physical distance within a given glioma correlates to genomic distance using multiple orthogonal genomic assessments. These data should be helpful in the clinical diagnostic and therapeutic management of glioma, for example by: managing sampling error, and estimating genetic heterogeneity using simple imaging inputs.

Correction to: Monitoring of intracerebellarly-administered natural killer cells with fluorine-19 MRI.

There was a typo in author Andrew Wahba's name in the initial online publication. The original article has been corrected.

Monitoring of intracerebellarly-administered natural killer cells with fluorine-19 MRI.

PURPOSE: Medulloblastoma (MB) is the most common malignant brain tumor in children. Recent studies have shown the ability of natural killer (NK) cells to lyse MB cell lines in vitro, but in vivo successes remain elusive and the efficacy and fate of NK cells in vivo remain unknown. METHODS: To address these questions, we injected MB cells into the cerebellum of immunodeficient mice and examined tumor growth at various days after tumor establishment via bioluminescence imaging. NK cells were labeled with a fluorine-19 (19F) MRI probe and subsequently injected either intratumorally or contralaterally to the tumor in the cerebellum and effect on tumor growth was monitored. RESULTS: The 19F probe efficiently labeled the NK cells and exhibited little cytotoxicity. Fluorine-19 MRI confirmed the successful and accurate delivery of the labeled NK cells to the cerebellum of the mice. Administration of 19F-labeled NK cells suppressed MB growth, with the same efficacy as unlabeled cells. Immunohistochemistry confirmed the presence of NK cells within the tumor, which was associated with induction of apoptosis in tumor cells. NK cell migration to the tumor from a distal location as well as activation of apoptosis was also demonstrated by immunohstochemistry. CONCLUSIONS: Our results show that NK cells present a novel opportunity for new strategies in MB treatment. Further, 19F-labeled NK cells can suppress MB growth while enabling 19F MRI to provide imaging feedback that can facilitate study and optimization of therapeutic paradigms.

Guiding the first biopsy in glioma patients using estimated Ki-67 maps derived from MRI: conventional versus advanced imaging.

BACKGROUND: Undersampling of gliomas at first biopsy is a major clinical problem, as accurate grading determines all subsequent treatment. We submit a technological solution to reduce the problem of undersampling by estimating a marker of tumor proliferation (Ki-67) using MR imaging data as inputs, against a stereotactic histopathology gold standard. METHODS: MR imaging was performed with anatomic, diffusion, permeability, and perfusion sequences, in untreated glioma patients in a prospective clinical trial. Stereotactic biopsies were harvested from each patient immediately prior to surgical resection. For each biopsy, an imaging description (23 parameters) was developed, and the Ki-67 index was recorded. Machine learning models were built to estimate Ki-67 from imaging inputs, and cross validation was undertaken to determine the error in estimates. The best model was used to generate graphical maps of Ki-67 estimates across the whole brain. RESULTS: Fifty-two image-guided biopsies were collected from 23 evaluable patients. The random forest algorithm best modeled Ki-67 with 4 imaging inputs (T2-weighted, fractional anisotropy, cerebral blood flow, Ktrans). It predicted the Ki-67 expression levels with a root mean square (RMS) error of 3.5% (R2 = 0.75). A less accurate predictive result (RMS error 5.4%, R2 = 0.50) was found using conventional imaging only. CONCLUSION: Ki-67 can be predicted to clinically useful accuracies using clinical imaging data. Advanced imaging (diffusion, perfusion, and permeability) improves predictive accuracy over conventional imaging alone. Ki-67 predictions, displayed as graphical maps, could be used to guide biopsy, resection, and/or radiation in the care of glioma patients.

The Emerging Role of Amino Acid PET in Neuro-Oncology.

Imaging plays a critical role in the management of the highly complex and widely diverse central nervous system (CNS) malignancies in providing an accurate diagnosis, treatment planning, response assessment, prognosis, and surveillance. Contrast-enhanced magnetic resonance imaging (MRI) is the primary modality for CNS disease management due to its high contrast resolution, reasonable spatial resolution, and relatively low cost and risk. However, defining tumor response to radiation treatment and chemotherapy by contrast-enhanced MRI is often difficult due to various factors that can influence contrast agent distribution and perfusion, such as edema, necrosis, vascular alterations, and inflammation, leading to pseudoprogression and pseudoresponse assessments. Amino acid positron emission tomography (PET) is emerging as the method of resolving such equivocal lesion interpretations. Amino acid radiotracers can more specifically differentiate true tumor boundaries from equivocal lesions based on their specific and active uptake by the highly metabolic cellular component of CNS tumors. These therapy-induced metabolic changes detected by amino acid PET facilitate early treatment response assessments. Integrating amino acid PET in the management of CNS malignancies to complement MRI will significantly improve early therapy response assessment, treatment planning, and clinical trial design.

Cytokine Response to Diet and Exercise Affects Atheromatous Matrix Metalloproteinase-2/9 Activity in Mice.

BACKGROUND: The aim of this study is to identify the principal circulating factors that modulate atheromatous matrix metalloproteinase (MMP) activity in response to diet and exercise.Methods and Results:Apolipoprotein-E knock-out (ApoE-/-) mice (n=56) with pre-existing plaque, fed either a Western diet (WD) or normal diet (ND), underwent either 10 weeks of treadmill exercise or had no treatment. Atheromatous MMP activity was visualized using molecular imaging with a MMP-2/9 activatable near-infrared fluorescent (NIRF) probe. Exercise did not significantly reduce body weight, visceral fat, and plaque size in either WD-fed animals or ND-fed animals. However, atheromatous MMP-activity was different; ND animals that did or did not exercise had similarly low MMP activities, WD animals that did not exercise had high MMP activity, and WD animals that did exercise had reduced levels of MMP activity, close to the levels of ND animals. Factor analysis and path analysis showed that soluble vascular cell adhesion molecule (sVCAM)-1 was directly positively correlated to atheromatous MMP activity. Adiponectin was indirectly negatively related to atheromatous MMP activity by way of sVCAM-1. Resistin was indirectly positively related to atheromatous MMP activity by way of sVCAM-1. Visceral fat amount was indirectly positively associated with atheromatous MMP activity, by way of adiponectin reduction and resistin elevation. MMP-2/9 imaging of additional mice (n=18) supported the diet/exercise-related anti-atherosclerotic roles for sVCAM-1. CONCLUSIONS: Diet and exercise affect atheromatous MMP activity by modulating the systemic inflammatory milieu, with sVCAM-1, resistin, and adiponectin closely interacting with each other and with visceral fat.

Hemophagocytic lymphohistiocytosis in adults: An under recognized entity.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of severe immune activation with macrophage and T-cell infiltration resulting in, multi organ damage. HLH may be primary or secondary in etiology. A high index of suspicion is essential for early diagnosis and treatment. Diagnostic criteria need to be refined and newer treatment options to be explored in order to improve survival especially in adult HLH and malignancy-associated HLH (M-HLH). We report a case of malignancy associated HLH (M-HLH) in adult treated on one of the only FDA-approved protocols for adult HLH to highlight the diagnostic and therapeutic challenges of this disease entity.

Dual-Energy Computed Tomography for the Characterization of Intracranial Hemorrhage and Calcification: A Systematic Approach in a Phantom System.

OBJECTIVE: The aim of this study was to develop a diagnostic framework for distinguishing calcific from hemorrhagic cerebral lesions using dual-energy computed tomography (DECT) in an anthropomorphic phantom system. MATERIALS AND METHODS: An anthropomorphic phantom was designed to mimic the CT imaging characteristics of the human head. Cylindrical lesion models containing either calcium or iron, mimicking calcification or hemorrhage, respectively, were developed to exhibit matching, and therefore indistinguishable, single-energy CT (SECT) attenuation values from 40 to 100 HU. These lesion models were fabricated at 0.5, 1, and 1.5 cm in diameter and positioned in simulated cerebrum and skull base locations within the anthropomorphic phantom. All lesion sizes were modeled in the cerebrum, while only 1.5-cm lesions were modeled in the skull base. Images were acquired using a GE 750HD CT scanner and an expansive dual-energy protocol that covered variations in dose (36.7-132.6 mGy CTDIvol, n = 12), image thickness (0.625-5 mm, n = 4), and reconstruction filter (soft, standard, detail, n = 3) for a total of 144 unique technique combinations. Images representing each technique combination were reconstructed into water and calcium material density images, as well as a monoenergetic image chosen to mimic the attenuation of a 120-kVp SECT scan. A true single-energy routine brain protocol was also included for verification of lesion SECT attenuation. Points representing the 3 dual-energy reconstructions were plotted into a 3-dimensional space (water [milligram/milliliter], calcium [milligram/milliliter], monoenergetic Hounsfield unit as x, y, and z axes, respectively), and the distribution of points analyzed using 2 approaches: support vector machines and a simple geometric bisector (GB). Each analysis yielded a plane of optimal differentiation between the calcification and hemorrhage lesion model distributions. By comparing the predicted lesion composition to the known lesion composition, we identified the optimal combination of CTDIvol, image thickness, and reconstruction filter to maximize differentiation between the lesion model types. To validate these results, a new set of hemorrhage and calcification lesion models were created, scanned in a blinded fashion, and prospectively classified using the planes of differentiation derived from support vector machine and GB methods. RESULTS: Accuracy of differentiation improved with increasing dose (CTDIvol) and image thickness. Reconstruction filter had no effect on the accuracy of differentiation. Using an optimized protocol consisting of the maximum CTDIvol of 132.6 mGy, 5-mm-thick images, and a standard filter, hemorrhagic and calcific lesion models with equal SECT attenuation (Hounsfield unit) were differentiated with over 90% accuracy down to 70 HU for skull base lesions of 1.5 cm, and down to 100 HU, 60 HU, and 60 HU for cerebrum lesions of 0.5, 1.0, and 1.5 cm, respectively. The analytic method that yielded the best results was a simple GB plane through the 3-dimensional DECT space. In the validation study, 96% of unknown lesions were correctly classified across all lesion sizes and locations investigated. CONCLUSIONS: We define the optimal scan parameters and expected limitations for the accurate classification of hemorrhagic versus calcific cerebral lesions in an anthropomorphic phantom with DECT. Although our proposed DECT protocol represents an increase in dose compared with routine brain CT, this method is intended as a specialized evaluation of potential brain hemorrhage and is thus counterbalanced by increased diagnostic benefit. This work provides justification for the application of this technique in human clinical trials.

Flow versus permeability weighting in estimating the forward volumetric transfer constant (Ktrans) obtained by DCE-MRI with contrast agents of differing molecular sizes.

PURPOSE: To quantify the differential plasma flow- (Fp-) and permeability surface area product per unit mass of tissue- (PS-) weighting in forward volumetric transfer constant (Ktrans) estimates by using a low molecular (Gd-DTPA) versus high molecular (Gadomer) weight contrast agent in dynamic contrast enhanced (DCE) MRI. MATERIALS AND METHODS: DCE MRI was performed using a 7T animal scanner in 14 C57BL/6J mice syngeneic for TRAMP tumors, by administering Gd-DTPA (0.9kD) in eight mice and Gadomer (35kD) in the remainder. The acquisition time was 10min with a sampling rate of one image every 2s. Pharmacokinetic modeling was performed to obtain Ktrans by using Extended Tofts model (ETM). In addition, the adiabatic approximation to the tissue homogeneity (AATH) model was employed to obtain the relative contributions of Fp and PS. RESULTS: The Ktrans values derived from DCE-MRI with Gd-DTPA showed significant correlations with both PS (r2=0.64, p=0.009) and Fp (r2=0.57, p=0.016), whereas those with Gadomer were found only significantly correlated with PS (r2=0.96, p=0.0003) but not with Fp (r2=0.34, p=0.111). A voxel-based analysis showed that Ktrans approximated PS (<30% difference) in 78.3% of perfused tumor volume for Gadomer, but only 37.3% for Gd-DTPA. CONCLUSIONS: The differential contributions of Fp and PS in estimating Ktrans values vary with the molecular weight of the contrast agent used. The macromolecular contrast agent resulted in Ktrans values that were much less dependent on flow. These findings support the use of macromolecular contrast agents for estimating tumor vessel permeability with DCE-MRI.

Kinetic Modeling and Constrained Reconstruction of Hyperpolarized [1-13C]-Pyruvate Offers Improved Metabolic Imaging of Tumors.

Hyperpolarized [1-(13)C]-pyruvate has shown tremendous promise as an agent for imaging tumor metabolism with unprecedented sensitivity and specificity. Imaging hyperpolarized substrates by magnetic resonance is unlike traditional MRI because signals are highly transient and their spatial distribution varies continuously over their observable lifetime. Therefore, new imaging approaches are needed to ensure optimal measurement under these circumstances. Constrained reconstruction algorithms can integrate prior information, including biophysical models of the substrate/target interaction, to reduce the amount of data that is required for image analysis and reconstruction. In this study, we show that metabolic MRI with hyperpolarized pyruvate is biased by tumor perfusion and present a new pharmacokinetic model for hyperpolarized substrates that accounts for these effects. The suitability of this model is confirmed by statistical comparison with alternates using data from 55 dynamic spectroscopic measurements in normal animals and murine models of anaplastic thyroid cancer, glioblastoma, and triple-negative breast cancer. The kinetic model was then integrated into a constrained reconstruction algorithm and feasibility was tested using significantly undersampled imaging data from tumor-bearing animals. Compared with naïve image reconstruction, this approach requires far fewer signal-depleting excitations and focuses analysis and reconstruction on new information that is uniquely available from hyperpolarized pyruvate and its metabolites, thus improving the reproducibility and accuracy of metabolic imaging measurements.

Differentiation of low-attenuation intracranial hemorrhage and calcification using dual-energy computed tomography in a phantom system.

OBJECTIVES: Calcific and hemorrhagic intracranial lesions with attenuation levels of less than 100 Hounsfield units (HUs) cannot currently be reliably differentiated by single-energy computed tomography (SECT). The proper differentiation of these lesion types would have a multitude of clinical applications. A phantom model was used to test the ability of dual-energy CT (DECT) to differentiate such lesions. MATERIALS AND METHODS: Agar gel-bound ferric oxide and hydroxyapatite were used to model hemorrhage and calcification, respectively. Gel models were scanned using SECT and DECT and organized into SECT attenuation-matched pairs at 16 attenuation levels between 0 and 100 HU. Dual-energy CT data were analyzed using 3-dimensional (3D) Gaussian mixture models (GMMs), as well as a simplified threshold plane metric derived from the 3D GMM, to assign voxels to hemorrhagic or calcific categories. Accuracy was calculated by comparing predicted voxel assignments with actual voxel identities. RESULTS: We measured 6032 voxels from each gel model, for a total of 193,024 data points (16 matched model pairs). Both the 3D GMM and its more clinically implementable threshold plane derivative yielded similar results, with higher than 90% accuracy at matched SECT attenuation levels of 50 HU and greater. CONCLUSIONS: Hemorrhagic and calcific lesions with attenuation levels between 50 and 100 HU were differentiable using DECT in a clinically relevant phantom system with higher than 90% accuracy. This method warrants further testing for potential clinical applications.

Change in postsurgical cavity size within the first 30 days correlates with extent of surrounding edema: consequences for postoperative radiosurgery.

OBJECTIVE: Resection cavity diameter of less than 40 mm is required to be eligible for stereotactic radiosurgery (SRS), after gross total resection of brain metastasis at our institution. Our study evaluates the correlation between vasogenic edema and change in cavity size for 30 days. METHODS: Cavity size was measured on the postoperative and follow-up magnetic resonance imaging. Vasogenic edema was quantified as the largest axial measurement of T2 hyperintensity surrounding the resection cavity (postoperative magnetic resonance imaging). RESULTS: Thirty-nine resection cavities (37 patients) were reviewed. There was a statistically significant (Pearson coefficient = -0.35; P = 0.02) negative correlation between edema and change in cavity size. An arbitrary cutoff value of a 15-mm edema yielded a sensitivity of 96% and a specificity of 65% (P < 0.001) to predict 10% decrease in cavity size. CONCLUSIONS: In patients with cavity size close to the size cutoff for SRS, rescanning closer to the date of SRS should be considered, especially if there is significant edema surrounding the cavity.

Molecular imaging detects impairment in the retrograde axonal transport mechanism after radiation-induced spinal cord injury.

PURPOSE: The goal of this study was to determine whether molecular imaging of retrograde axonal transport is a suitable technique to detect changes in the spinal cord in response to radiation injury. PROCEDURES: The lower thoracic spinal cords of adult female BALB/c mice were irradiated with single doses of 2, 10, or 80 Gy. An optical imaging method was used to observe the migration of the fluorescently labeled nontoxic C-fragment of tetanus toxin (TTc) from an injection site in the calf muscles to the spinal cord. Changes in migration patterns compared with baseline and controls allowed assessment of radiation-induced alterations in the retrograde neuronal axonal transport mechanism. Subsequently, tissues were harvested and histological examination of the spinal cords performed. RESULTS: Transport of TTc in the thoracic spinal cord was impaired in a dose-dependent manner. Transport was significantly decreased by 16 days in animals exposed to either 10 or 80 Gy, while animals exposed to 2 Gy were affected only minimally. Further, animals exposed to the highest dose also experienced significant weight loss by 9 days and developed posterior paralysis by 45 days. Marked histological changes including vacuolization, and white matter necrosis were observed in radiated cords after 30 days for mice exposed to 80 Gy. CONCLUSION: Radiation of the spinal cord induces dose-dependent changes in retrograde axonal transport, which can be monitored by molecular imaging. This approach suggests a novel diagnostic modality to assess nerve injury and monitor therapeutic interventions.