Dick J. Drost

Mapping Corpus Callosum Deficits in Autism: An Index of Aberrant Cortical Connectivity

BACKGROUND Volumetric studies have reported reductions in the size of the corpus callosum (CC) in autism, but the callosal regions contributing to this deficit have differed among studies. In this study, a computational method was used to detect and map the spatial pattern of CC abnormalities in male patients with autism. METHODS Twenty-four boys with autism (aged 10.0 +/- 3.3 years) and 26 control boys (aged 11.0 +/- 2.5 years) underwent a magnetic resonance imaging (MRI) scan at 3 Tesla. Total and regional areas of the CC were determined using traditional morphometric methods. Three-dimensional (3D) surface models of the CC were also created from the MRI scans. Statistical maps were created to visualize morphologic variability of the CC and to localize regions of callosal thinning in autism. RESULTS Traditional morphometric methods detected a significant reduction in the total callosal area and in the anterior third of the CC in patients with autism; however, 3D maps revealed significant reductions in both the splenium and genu of the CC in patients. CONCLUSIONS Statistical maps of the CC revealed callosal deficits in autism with greater precision than traditional morphometric methods. These abnormalities suggest aberrant connections between cortical regions, which is consistent with the hypothesis of abnormal cortical connectivity in autism.

Simultaneous MRI Measurement of Blood Flow, Blood Volume, and Capillary Permeability in Mammary Tumors Using Two Different Contrast Agents

A technique for the simultaneous measurement of three vascular parameters: blood flow (Fρ), blood volume (vb), and the capillary permeability‐surface area product (PSρ) in breast tumors using dynamic contrast‐enhanced magnetic resonance imaging (MRI) is presented. Features of the technique include measurement of precontrast tumor T1, rapid temporal sampling, measurement of the arterial input function, and use of a distributed parameter tracer kinetic model. Parameter measurements are compared that were determined using two contrast agents of different molecular weights, gadolinium‐diethylene triamine pentaacetic acid (Gd‐DTPA; 0.6 kDa) and Gadomer‐17 (17 kDa), in 18 spontaneous canine mammary tumors. Measurements of Fρ and vb corresponded well with literature values, and the mean PSρ measured using Gd‐DTPA was a factor of 15 higher than that measured using Gadomer‐17. J. Magn. Reson. Imaging 2000;12:991–1003.

Comparison of the quantification precision of human short echo time 1H spectroscopy at 1.5 and 4.0 Tesla

Precise quantification of human in vivo short echo time 1H spectra remains problematic at clinical field strengths due to broad peak linewidths and low signal‐to‐noise ratio (SNR). In this study, multiple STEAM spectra (TE = 20 ms, volume = 8 cm3) were acquired in a single individual at 1.5 T and 4 T to compare quantification precision. Test–retest STEAM spectra (volume = 1.5 cm3) were also acquired from the anterior cingulate and thalamus of 10 individuals at 4.0 T. Metabolite levels were quantified using automated software that incorporated field strength‐specific prior knowledge. With the distinct methods of data acquisition, processing, and fitting used in this study, peak height SNR increased ∼80% while peak linewidth increased by ∼50% in the 8 cm3 volumes at 4.0 T compared to 1.5 T, resulting in an average increase in quantification precision of 39%. Metabolite levels from test–retest data (1.5 cm3 voxels at 4.0 T) were quantified with similar inter‐ and intraindividual variability. Magn Reson Med 44:185–192, 2000. Published 2000 Wiley‐Liss, Inc.

A 4.0-T fMRI study of brain connectivity during word fluency in first-episode schizophrenia

OBJECTIVE To use functional magnetic resonance imaging (fMRI) to investigate functional connectivity, and hence, underlying neural networks, in never-treated, first-episode patients with schizophrenia using a word fluency paradigm known to activate prefrontal, anterior cingulate, and thalamic regions. Abnormal connectivity between the prefrontal cortex (PFC) and other brain regions has been demonstrated in chronic, medicated patients in previous positron emission tomography (PET) studies, but has not to our knowledge, previously been demonstrated using both first-episode, drug-naïve patients and fMRI technology. METHODS A 4.0-Tesla (T) fMRI was used to examine activation and functional connectivity [psychophysiological interactions (PPIs)] during a word fluency task compared to silent reading in 10 never-treated, first-episode patients with schizophrenia and 10 healthy volunteers of comparable age, sex, handedness, and parental education. RESULTS Compared to healthy volunteers, the schizophrenia patient group exhibited less activation during the word fluency task, mostly in the right anterior cingulate and prefrontal regions. Psychophysiological interactions between right anterior cingulate and other parts of the brain revealed a localized interaction with the left temporal lobe in healthy volunteers during the task and a widespread unfocussed interaction in patients. CONCLUSION These findings suggest anterior cingulate involvement in the neuronal circuitry underlying schizophrenia.

Factors affecting the quantification of short echo in-vivo 1H MR spectra: prior knowledge, peak elimination, and filtering.

Short echo 1H in‐vivo brain MR spectra are difficult to quantify for several reasons: low signal to noise ratio, the severe overlap of spectral lines, the presence of macromolecule resonances beneath the resonances of interest, and the effect of resonances adjacent to the spectral region of interest (SRI). This paper outlines several different quantification strategies and the effect of each on the precision of in‐vivo metabolite measurements. In‐vivo spectra were quantified with no operator interaction using a template of prior knowledge determined by mathematically modeling separate in‐vitro metabolite spectra. Metabolite level estimates and associated precision were compared before and after the inclusion of macromolecule resonances as part of the prior knowledge, and following two different methods of handling resonances adjacent to the SRI. The effects of rectangular and exponential filters were also investigated. All methods were tested using repeated in‐vivo spectra from one individual acquired at 1.5 T using stimulated echo acquisition mode (STEAM, TE = 20 ms) localization. The results showed that the inclusion of macromolecules in the prior knowledge was necessary to obtain metabolite levels consistent with the literature, while the fitting of resonances adjacent to the SRI concurrent with modeled metabolites optimized the precision of metabolite estimates. Metabolite levels and precision were also affected by rectangular and exponential filtering, suggesting caution must be taken when such filters are used. Copyright

Evidence for Cortical Dysfunction in Autism: A Proton Magnetic Resonance Spectroscopic Imaging Study

BACKGROUND Although brain imaging studies have reported neurobiological abnormalities in autism, the nature and distribution of the underlying neurochemical irregularities are unknown. The purpose of this study was to examine cerebral gray and white matter cellular neurochemistry in autism with proton magnetic resonance spectroscopic imaging (MRSI). METHODS Proton MRSI examinations were conducted in 26 males with autism (age 9.8 +/- 3.2 years) and 29 male comparison subjects (age 11.1 +/- 2.4 years). Estimates of cerebral gray and white matter concentrations of N-acetylaspartate (NAA), creatine + phosphocreatine, choline-containing compounds, myo-inositol, and glutamate + glutamine (Glx) were made by linear regression analysis of multi-slice MRSI data and compared between groups. Regional estimates of metabolite concentration were also made with multivariate linear regression, allowing for comparisons of frontal, temporal, and occipital gray matter, cerebral white matter, and the cerebellum. RESULTS Patients with autism exhibited significantly lower levels of gray matter NAA and Glx than control subjects. Deficits were widespread, affecting most cerebral lobes and the cerebellum. No significant differences were detected in cerebral white matter or cerebellar metabolite levels. CONCLUSIONS These results suggest widespread reductions in gray matter neuronal integrity and dysfunction of cortical and cerebellar glutamatergic neurons in patients with autism.

Proton magnetic resonance spectroscopy in the brain: report of AAPM MR Task Group #9.

AAPM Magnetic Resonance Task Group #9 on proton magnetic resonance spectroscopy (MRS) in the brain was formed to provide a reference document for acquiring and processing proton (1H) MRS acquired from brain tissue. MRS is becoming a common adjunct to magnetic resonance imaging (MRI), especially for the differential diagnosis of tumors in the brain. Even though MR imaging is an offshoot of MR spectroscopy, clinical medical physicists familiar with MRI may not be familiar with many of the common practical issues regarding MRS. Numerous research laboratories perform in vivo MRS on other magnetic nuclei, such as 31P, 13C, and 19F. However, most commercial MR scanners are generally only capable of spectroscopy using the signals from protons. Therefore this paper is of limited scope, giving an overview of technical issues that are important to clinical proton MRS, discussing some common clinical MRS problems, and suggesting how they might be resolved. Some fundamental issues covered in this paper are common to many forms of magnetic resonance spectroscopy and are written as an introduction for the reader to these methods. These topics include shimming, eddy currents, spatial localization, solvent saturation, and post-processing methods. The document also provides an extensive review of the literature to guide the practicing medical physicist to resources that may be useful for dealing with issues not covered in the current article.

Membrane phospholipid metabolism and schizophrenia: an in vivo 31P-MR spectroscopy study

Membrane phospholipid metabolism was studied with 31P magnetic resonance spectroscopy in the left dorsal prefrontal cortex of 19 male, medicated, schizophrenic patients and compared to 18 normal male controls matched in age, education and parental education level. The schizophrenic patients had significantly decreased phosphomonoester levels (PMEs, metabolites predominantly involved in the synthesis of membrane phospholipids). Phosphodiester levels (PDEs, breakdown products of membrane phospholipids) were not statistically different in schizophrenic patients compared to controls. However, a significant increase in the PDE levels was observed in the newly diagnosed patient subgroup. This observed pattern of the PMEs and PDEs would be consistent with the presence of an abnormal neurodevelopment early in the illness of schizophrenia.

Detection and mapping of hippocampal abnormalities in autism

Brain imaging studies of the hippocampus in autism have yielded inconsistent results. In this study, a computational mapping strategy was used to examine the three-dimensional profile of hippocampal abnormalities in autism. Twenty-one males with autism (age: 9.5+/-3.3 years) and 24 male controls (age: 10.3+/-2.4 years) underwent a volumetric magnetic resonance imaging scan at 3 Tesla. The hippocampus was delineated, using an anatomical protocol, and hippocampal volumes were compared between the two groups. Hippocampal traces were also converted into three-dimensional parametric surface meshes, and statistical brain maps were created to visualize morphological differences in the shape and thickness of the hippocampus between groups. Parametric surface meshes and shape analysis revealed subtle differences between patients and controls, particularly in the right posterior hippocampus. These deficits were significant even though the groups did not differ significantly with traditional measures of hippocampal volume. These results suggest that autism may be associated with subtle regional reductions in the size of the hippocampus. The increased statistical and spatial power of computational mapping methods provided the ability to detect these differences, which were not found with traditional volumetric methods.

A short echo proton magnetic resonance spectroscopy study of the left mesial-temporal lobe in first-onset schizophrenic patients

BACKGROUND Past 1H magnetic resonance spectroscopy (MRS) studies of the temporal lobe in schizophrenic patients have shown decreased levels of N-acetylaspartate (NAA) suggesting reduced neuronal density in this region. However, the measured volumes have been large and included contributions from mostly white matter. METHODS Short echo 1H MRS was used to measure levels of NAA and other metabolites (i.e., glutamate and glutamine) from a 6 cm3 volume in the left mesial-temporal lobe of 11 first-episode schizophrenic patients and 11 healthy control subjects of comparable age, gender, handedness, education, and parental education levels. Spectra were quantified without operator interaction using automated software developed in our laboratory. Metabolite levels were normalized to the internal water concentration of each volume studied. Images were also obtained to determine temporal lobe gray and white matter volumes. RESULTS No significant differences were found between levels of NAA or other metabolites, or gray and white matter volumes, in first-episode schizophrenic patients and comparison subjects. CONCLUSIONS Since the volume studied was small compared to previous studies and contained mostly gray matter, this result suggests consequential NAA decreases may be restricted to regions of white matter.