Denise Davis

Magnetic Resonance Imaging of Children Without Sedation: Preparation With Simulation

OBJECTIVE It was hypothesized that a scanner simulator that replicates the magnetic resonance imaging (MRI) environment could be used to prepare pediatric subjects for successful completion of a diagnostic-quality MRI examination without pharmacological sedation. METHOD Sixteen healthy children, 6 to 17 years of age, were matched for age and sex with 16 psychotropic medication-naive children with obsessive-compulsive disorder. Distress was measured throughout simulation and scanning procedures using heart rate and a self-report distress scale. Ten healthy children, 6 to 17 years of age, also underwent the same actual MRI scanning procedure but did not undergo the simulation scanning procedure. RESULTS Significant decreases in heart rate and self-reported distress level were observed in all subjects during the simulator session that were maintained to the end of the actual scanner experience. All subjects successfully completed MRI examinations without chemical restraint. Subjects who were not trained in the simulator had higher heart rates and self-reported distress levels in the actual scanner than did simulation-trained subjects. CONCLUSIONS Simulation without pharmacological sedation successfully prepared pediatric subjects in this pilot study for high-quality MRI studies. Subject preparation may be an alternative procedure to sedation for routine MRI examination in healthy and anxious children 6 years of age and older.

Quantitative tissue sodium concentration mapping of the growth of focal cerebral tumors with sodium magnetic resonance imaging.

Tissue sodium concentration (TSC), as determined by in vivo 23Na magnetic resonance imaging (MRI) and the ex vivo classical 22Na radionuclide dilution assay (RDA), has been compared in a rat model of a focal glioma. The 23Na MRI method used a three‐dimensional, twisted projection acquisition scheme at short echo time to minimize signal losses from relaxation of transverse magnetization. Calibration standards within the field of view allowed quantification of the sodium signal in terms of a TSC after correction for B1 nonuniformity and tissue water concentration. The 23Na MRI method measured focally increased TSC values in tumors that were equivalent statistically to the destructive 22Na RDA method. The noninvasive 23Na MRI method provided a quantitative means with which to monitor focal brain tumor growth. Magn Reson Med 41:351–359, 1999.

2D and 3D 3-tesla magnetic resonance imaging of the double bundle structure in anterior cruciate ligament anatomy

For anterior cruciate ligament (ACL) surgery using the anatomic approach of the double bundle concept it is helpful to describe the anteromedial (AM) and posterolateral (PL) bundle using Magnetic Resonance Imaging (MRI), since this is the most important preoperative parameter next to the physical examination. The aim of this study was to distinguish both bundles in MRI. In a prospective study we evaluated the double bundle structure in ACL anatomy with a 3-T ultra-high-field strength MR imaging of cadaver knees, which allows faster imaging times, increased resolution and increased signal-to-noise ratio. Using oblique sagittal and oblique coronal planes, we were able to distinguish the double bundle structure in each knee. The following arthroscopic evaluation of the knees confirmed our MRI findings. Our study demonstrates the possibility of distinguishing the two bundles in the native ACL with 3T MRI. Following examinations must study the value for clinical application by describing different rupture patterns of the bundles and correlating this to arthroscopy. It would be advantageous to know the rupture pattern in advance. Presurgical planning could be improved by reconstructing only the torn and preserving the intact bundle.

PET imaging of brain macrophages using the peripheral benzodiazepine receptor in a macaque model of neuroAIDS.

HIV infection in humans and simian immunodeficiency virus (SIV) infection in macaques result in encephalitis in approximately one-quarter of infected individuals and is characterized by infiltration of the brain with infected and activated macrophages. 1-(2-chlorphenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide (PK11195) is a ligand specific for the peripheral benzodiazepine receptor abundant on macrophages and is expressed in low levels in the noninfected brain. We hypothesized that positron-emission tomography (PET) with the carbon-11-labeled, R-enantiomer form of PK11195 ([(11)C](R)-PK11195) could image brain macrophages and hence the development of encephalitis in vivo. [(11)C](R)-PK11195 binding was assessed in the brain using PET in 11 SIV infected macaques, six of which showed increased binding in vivo. Postmortem examination of the brain in these six macaques demonstrated encephalitis, while macaques that did not show an increase in [(11)C](R)-PK11195 binding did not develop SIV encephalitis. Brain tissue from SIV encephalitic macaques also showed increased [(3)H](R)-PK11195 binding compared with binding in nonencephalitic macaques. Increased PK11195 binding in vivo and in postmortem brain tissue correlated with abundance of macrophages but not astrocytes. Our results suggest that PET [(11)C](R)-PK11195 imaging can detect the presence of macrophages in SIV encephalitis in vivo and may be useful to predict the development of HIV encephalitis and in studies of the pathogenesis and treatment of HIV dementia.

3-T MR imaging of partial ACL tears: a cadaver study

Magnetic resonance imaging (MRI) is the most commonly used diagnostic imaging procedure for suspected injuries to the anterior cruciate ligament (ACL). However, MRI has less utility for the evaluation of partial ACL tears. The goal of this study was to evaluate the possibility of distinguishing partial ACL tears applying the double bundle concept by dividing the ACL anatomy in the anteromedial (AM) and posterolateral bundle (PL). Six human cadaver knees were used in this laboratory study. The protocol consisted of sagittal, oblique coronal, and oblique sagittal proton-density-weighted fast spin echo sequences. After MRI the AM and the PL bundle were severed to mimic different partial ACL rupture patterns. MRI scanning of each knee was repeated, to record the quantitative parameters tilt and ACL angles and discontinuity as a nonquantitative parameter. Three orthopaedic surgeons and two radiologists were enlisted as blinded observers to evaluate the images. The transection patterns could be differentiated by evaluating discontinuity both in the paracoronal and in the sagittal plane. Evaluating the transection patterns, the AM bundle reached a better result in both planes compared to the PL bundle and the paracoronal plane had a better result in assessing the transection patterns compared to the sagittal plane for the PL bundle. Partial ACL transections could predictably be recognized on oblique sagittal and oblique coronal planes utilizing 3-T MRI technology. This concept allows a more precise description of ACL rupture patterns and might lead to a more distinctive approach for reconstructive surgery. The presurgical planning could be improved by applying a treatment algorithm based on a description of each bundle as intact or ruptured, leading to a reconstruction of the torn and a preservation of the intact bundle.

Clinical fMRI: implementation and experience.

Functional magnetic resonance imaging (fMRI) is a new tool for understanding how the brain performs cognitive functions. Paradigms of increasing sophistication such as language comprehension (Just et al., 1996a), visuospatial processing (Just et al., 1996b), and working memory (Sweeney et al., 1996a,b,c) move beyond the simple visual and motor tasks that were used to establish the robustness of the technique (Thulborn et al., 1995, 1996a,b,c,d). Not only does this technique allow the location of cognitive functions to be mapped to discrete but distributed regions of the brain but it also examines how the brain copes with tasks of increasing demands by recruiting new resources from other regions and sequencing processes across multiple regions according to the task (Just et al., 1996b; Thulborn et al., 1996a,b,c,d). A complete historical introduction of fMRI is not the purpose of this report but rather it focuses on the extension of investigations on normal volunteers in which the basic cerebrovascular physiology is assumed to be constant across individuals to patients with pathology that arise from abnormal cerebrovascular physiology. Such clinical applications are challenging because of the need to perform the study as safely and as efficiently as possible in a subject who is often distracted and anxious about his or her illness. The interpretation of the results in the setting of altered physiology must be ambiguous unless the hemodynamic and metabolic status of the brain is characterized. Technical failures must be minimized and results must be available quickly if clinical utility is to be established. The design of equipment that meets these constraints of clinical fMRI and our initial experience with patients will be described.

Comparison of proton magnetic resonance spectroscopy with fluorine-18 2-fluoro-deoxyglucose positron emission tomography for assessment of brain tumor progression

We investigated the accuracy of high‐field proton magnetic resonance spectroscopy (1H MRS) and fluorine‐18 2‐fluoro‐deoxyglucose positron emission tomography (18F‐FDG‐PET) for diagnosis of glioma progression following tumor resection, stereotactic radiation, and chemotherapy.

Combined imaging biomarkers for therapy evaluation in glioblastoma multiforme: correlating sodium MRI and F-18 FLT PET on a voxel-wise basis

We evaluate novel magnetic resonance imaging (MRI) and positron emission tomography (PET) quantitative imaging biomarkers and associated multimodality, serial-time-point analysis methodologies, with the ultimate aim of providing clinically feasible, predictive measures for early assessment of response to cancer therapy. A focus of this work is method development and an investigation of the relationship between the information content of the two modalities. Imaging studies were conducted on subjects who were enrolled in glioblastoma multiforme (GBM) therapeutic clinical trials. Data were acquired, analyzed and displayed using methods that could be adapted for clinical use. Subjects underwent dynamic [(18)F]fluorothymidine (F-18 FLT) PET, sodium ((23)Na) MRI and 3-T structural MRI scans at baseline (before initiation of therapy), at an early time point after beginning therapy and at a late follow-up time point after therapy. Sodium MRI and F-18 FLT PET images were registered to the structural MRI. F-18 FLT PET tracer distribution volumes and sodium MRI concentrations were calculated on a voxel-wise basis to address the heterogeneity of tumor physiology. Changes in, and differences between, these quantities as a function of scan timing were tracked. While both modalities independently show a change in tissue status as a function of scan time point, results illustrate that the two modalities may provide complementary information regarding tumor progression and response. Additionally, tumor status changes were found to vary in different regions of tumor. The degree to which these methods are useful for GBM therapy response assessment and particularly for differentiating true progression from pseudoprogression requires additional patient data and correlation of these imaging biomarker changes with clinical outcome.

Molecular and metabolic pattern classification for detection of brain glioma progression.

OBJECTIVES The ability to differentiate between brain tumor progression and radiation therapy induced necrosis is critical for appropriate patient management. In order to improve the differential diagnosis, we combined fluorine-18 2-fluoro-deoxyglucose positron emission tomography ((18)F-FDG PET), proton magnetic resonance spectroscopy ((1)H MRS) and histological data to develop a multi-parametric machine-learning model. METHODS We enrolled twelve post-therapy patients with grade 2 and 3 gliomas that were suspicious of tumor progression. All patients underwent (18)F-FDG PET and (1)H MRS. Maximal standardized uptake value (SUVmax) of the tumors and reference regions were obtained. Multiple 2D maps of choline (Cho), creatine (Cr), and N-acetylaspartate (NAA) of the tumors were generated. A support vector machine (SVM) learning model was established to take imaging biomarkers and histological data as input vectors. A combination of clinical follow-up and multiple sequential MRI studies served as the basis for assessing the clinical outcome. All vector combinations were evaluated for diagnostic accuracy and cross validation. The optimal cutoff value of individual parameters was calculated using Receiver operating characteristic (ROC) plots. RESULTS The SVM and ROC analyses both demonstrated that SUVmax of the lesion was the most significant single diagnostic parameter (75% accuracy) followed by Cho concentration (67% accuracy). SVM analysis of all paired parameters showed SUVmax and Cho concentration in combination could achieve 83% accuracy. SUVmax of the lesion paired with SUVmax of the white matter as well as the tumor Cho paired with the tumor Cr both showed 83% accuracy. These were the most significant paired diagnostic parameters of either modality. Combining all four parameters did not improve the results. However, addition of two more parameters, Cho and Cr of brain parenchyma contralateral to the tumor, increased the accuracy to 92%. CONCLUSION This study suggests that SVM models may improve detection of glioma progression more accurately than single parametric imaging methods. RESEARCH SUPPORT National Cancer Institute, Cancer Center Support Grant Supplement Award, Imaging Response Assessment Teams.

Non-invasive assessment of tumor proliferation using triple quantum filtered /sup 23/Na MRI: technical challenges and solutions

We address the development of triple-quantum-filtered sodium MRI as a non-invasive surrogate measure for cell proliferation in brain tumors. We demonstrate that through careful consideration of the theoretical description of the signal, triple-quantum-filtered sodium images of adequate signal-to-noise ratio (SNR) can be acquired in clinically acceptable imaging times.