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Brain Morphology (MRC-116)
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Summary
In the human brain morphology project, we
will characterize the human brain tissue in schizophrenic patients
and healthy subjects using high resolution magnetic resonance imaging
and computerized image analysis methods. This includes measurement
of different brain structures/volumes, the determination of white
matter organization (determination of regional axonal connectivity)
and the characteristics of the brain surface. The aim is to generate
high precision quantitative data with respect to neuroanatomical
characteristics in a large number of individuals.
Project aims
1) To measure the volumes of anatomical brain
structures from volumetric MRI scans. This involves segmentation
of brain tissue (i.e. automated classification of brain tissue into
gray and white matter, and cerebrospinal fluid (CSF) volumes), and
the manual/automatic delineation of anatomical structures. 2) To
analyze brain surface with respect to gyrification and sulcification
patterns. 3) To characterize white matter organization with MR diffusion
tensor anisotropy. 4) To develop new methods that will facilitate
the above mentioned aims.
Background
Wernicke in 1894 originally proposed that
psychotic disorders arise from pathological changes in circuits
or networks of anatomically interconnected brain regions. For instance,
it has been reported that patients with schizophrenia demonstrate
abnormally connected or ”functionally dysconnected” regional
cerebral blood flow changes between left dorsolateral prefrontal
cortex and bilateral superior temporal gyri during performance of
a word generation task. The functional dysconnectivity of the prefrontal-temporal
axis may be anatomically determined. Other models of dysfunction
include the neurodevelopmental models for the pathogenesis of schizophrenia.
The neurodevelopmental models have been suggested to encompass at
least two independent processes based on different combinations
of genetic and perinatal influences. In the neuroimaging literature
on brain changes in schizophrenia, changes in global anatomical
measures such as reduced cerebral volume, reduced cortical gray
matter and increased ventricle-to-brain ratio have been reported.
Regional reductions have been demonstrated for several brain structures
such as the hippocampus, parahippocampal gyrus, amygdala, superior
temporal gyrus, frontal cortex, thalamus, and the cerebellum. There
have been attempts to find a unifying concept behind the diversity
of signs and symptoms in schizophrenia as well as the neuroanatomic/functional
abnormalities. Thus, abnormalities in the cortico-cerebellar-thalamic-cortical
circuitry have been proposed as well as global changes in the gray
matter/ventricular system and a supra-regional change in the frontal-temporal
system. It has been suggested that the neuroanatomic abnormality
in schizophrenia consists of strategically localized, left-lateralized
reductions of gray matter, especially in the temporal lobe. A meta-analysis
of 58 studies demonstrated global structural differences between
patients with schizophrenia and nonschizophrenic comparison subjects:
cerebral volume was smaller and total ventricular volume was larger.
Regional volume reductions in excess of these global differences
were particularly marked in the bilateral medial temporal regions.
Methodology
The subjects are investigated in a high resolution
1.5 Tesla GE signa (Milwaukee, Wis.) system at the MR Research Center,
Karolinska Hospital, Stockholm, Sweden. Selected pulse sequences
are used in one scanning session with a total time duration of approximately
50 minutes. MR data analyses (automated segmentation, manual/automated
delineation and brain surface characterization) are performed at
the Karolinska Institute using the software BRAINS at the courtesy
of Prof. Nancy C. Andreasen, Mental Health Clinical Research Center,
The University
of Iowa College of Medicine and Hospitals and Clinics, Iowa City
52242, USA. From two sets of segmented (discrete and continuous)
cranial volumes from each subject, we measure total intracranial
volume and a series of "Talairach boxes" comprising larger
anatomical structures. The caudate, putamen, thalamus and the hippocampus
are delineated using artificial neural nets or manual outlining.
A method for the parcellation of the cerebellar vermis has been
developed.
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Figure 1
(for larger image, click on it)
Figure 1 demonstrates the BRAINS interface
of a segmented human brain in axial, coronal and sagittal
projections. The colored outlines are traces from ANNs of
the intracranial volume (red), caudate nucleus and putamen
(both green and purple) and the hippocampus (yellow).
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MR physicist Stefan Skare, Karolinska Institute,
developed the pulse sequences for the diffusion tensor. All subjects
are investigated with diffusion tensor sequences. Over the past
year over 100 examinations have been performed. The results of inter-
and intrareliability testings for the classification procedure as
well as for the manual outlining of the cerebellar vermis and hemispheres
with the current program have been excellent (10 scans; ICC>.96).
We presently test the consistency of segmentation, difffusion tensor
and cerebellar vermis measures over time.
References
Wright IC, Sharma T, Ellison ZR, McGuire PK, Friston KJ, Brammer
MJ, Murray RM, Bullmore ET. Supra-regional brain systems and the
neuropathology of schizophrenia. Cerebral Cortex. 1999; 9: 366-378
Wright IC, Rabe-Hesketh S, Woodruff PWR, David AS, Murray RM, Bullmore
ET. Meta-analysis of regional brain volumes in schizophrenia. Am
J Psychiatry. 2000; 157(1): 16-25.
Nelson MD, Saykin AJ, Flashman LA, Riordan HI. Hipocampal volume
reduction in schizophrenia as assessed by magnetic resonance imaging.
Arch Gen Psychiatry. 1998; 55:433-440.
Shenton ME, Kikinis R, Jolesz FA, Pollak SD, Lemay M, Wible CG,
Hokama H, Martin J, Metcalf D, Coleman M, McCarley RW. Left tempotral
lobe abnormalities in schizophrenia and thought disorder: A quantitative
study.
Andreasen NC. A unitary model of schizophrenia. Bleuler’s ”fragmented
phrene” as schizencephaly. Arch Gen Psychiatry. 1999; 56: 781-787.
Andreasen NC. Understanding the causes of schizophrenia.N Engl J
Med. 1999; 340(8): 645-7.
Andreasen NC, O’Leary DS, Flaum M, Nopoulos P, Watkins GL,
Boles-Ponto LL, Hichwa RD. Hypofrontality in schizophrenia: distribution
of dysfunctional circuits in neuroleptic-naive patients. Lancet
1997: 349: 1730-1734.
Andreasen NC, Rajarethinam R, Cizadlo T, Arndt S, Swayze VW II,
Flashman LA, O’Leary DS, Ehrhardt JC, Yuh WTC. Automatic atlas-based
volume estimation of human brain regions from MR images. J Comp
Ass Tomography. 1996; 20(1) 98-106.
Magnotta VA, Andreasen NC, Schultz SK, Harris G, Cizadlo T, Heckel
D, Nopoulos P, Flaum. Quantitative in vivo measurement of gyrification
in the human brain: changes associated with aging. Cereb Cortex.
1999; 9(2): 151-60.
Magnotta VA, Heckel D, Andreasen NC, Cizadlo T, Corson PW, Ehrhardt
JC, Yuh WT. Measurement of brain structures with artificial neural
networks: two- and three-dimensional applications. Radiology. 1999;
211(3):781-90.
Project leader: Ingrid
Agartz
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