Brain Landmarks Research Articles

Landmark‐Based Shape Analysis of the Brain: An Error Study

Neuroanatomic phenotypes are often assessed using volumetric analysis. Although powerful and versatile, this approach is unable to 1) determine whether changes in size are global or local, 2) quantify changes in shape, or 3) describe how regions are interrelated. Statistical shape analysis is the preferred method for testing these aspects of phenotype. Coordinate data from biologically relevant landmarks are one commonly used way to quantify “shape” of an object. To date, approximately fifty landmarks have been used to study brain shape. Of the studies that used landmark‐based statistical shape analysis on the brain, most have not published the protocols they used for landmark identification or the results of reliability studies on these landmarks. The primary aims of this study were two‐fold: (1) to collaboratively develop detailed protocols for a set of brain landmarks, and (2) to complete an inter‐observer (n = 4) validation study of the set of landmarks on 10 MR scans of three trials each. Detailed protocols were developed for 29 cortical and subcortical landmarks. MANOVA revealed that this set of landmarks was able to accurately distinguish between individuals (p < 0.01). Precision varied between 0.71 – 6.50 mm. This was the first study to quantitatively assess landmarks for use in statistical shape analysis of the brain and documents the utility of landmark data for studies of neuroanatomic phenotypes.Grant Funding Source: NIDCR 1F31DE021302‐01

Detection of MPTP-Induced Substantia Nigra Hyperechogenicity in Rhesus Monkeys by Transcranial Ultrasound

Detection of substantia nigra (SN) hyperechogenicity by transcranial ultrasound has been proposed as a putative biomarker to differentiate between idiopathic Parkinson's disease (PD) and other forms of parkinsonism. In the present study, we evaluated the feasibility of using transcranial ultrasound to detect SN echogenicity in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated Rhesus monkeys, a well-established model of PD. All animals had natural temporal bone windows for transcranial sonography. We could show that it is possible to visualize major brain landmarks including the “butterfly shaped” midbrain, basal cisterns, third and lateral ventricles in all animals by transcranial ultrasound. Blinded assessments showed that all normal monkeys had no SN hyperechogenicity. Bilaterally parkinsonian (overlesioned) monkeys showed hyperechogenicity of both SN, whereas right hemiparkinsonian monkeys only showed left nigral hyperechogenicity. These findings confirm the feasibility of transcranial ultrasound to detect SN hyperechogenicity in MPTP-treated Rhesus monkeys and suggest that this animal model may provide a platform for understanding the pathophysiologic basis of nigral hyperechogenicity. (E-mail: tsubram@yahoo.com)

Assessment of the variability in the anatomical position and size of the subthalamic nucleus among patients with advanced Parkinson’s disease using magnetic resonance imaging

Targeting of the subthalamic nucleus (STN) during deep brain stimulation (DBS) surgery using standard atlas coordinates is used in some centers. Such coordinates are accurate for only a subgroup of patients, and subgroup size depends on the extent of inter-individual variation in STN position/size and degree to which atlas represents average anatomical relations. Few studies have addressed this issue. Sixty-two axial T(2)-weighted magnetic resonance (MR) images of the brain (1.5 T) were obtained before STN-DBS in 62 patients (37 males) with Parkinson's disease using a protocol optimized for STN visualization. Image distortion was within sub-millimeter range. Midcommissural point (MCP)-derived coordinates of STN borders, STN center, and other brain landmarks were obtained using stereotactic software. MR-derived measurements were compared to Schaltenbrand and Wahren Atlas. We evaluated 117 best-visualized STNs. STN dimensions and coordinates of its center were highly variable. STN lateral coordinate ranged 8.7 mm-14.5 mm from MCP, A-P coordinate 3.5 mm posterior to 0.5 mm anterior to MCP, and vertical coordinate 1.3 mm-6 mm below MCP. The antero-posterior nucleus dimension varied by 8 mm and lateral-medial dimension by 5.8 mm. Differences between mean values of MR-derived data sets and Atlas values were statistically significant but moderate, excluding AC-PC length, for which the Atlas value was below the 1st percentile of the MR data set. The STN lateral coordinate strongly correlated with the width of the third ventricle (r = 0.73, p < 0.001). It is now possible to directly evaluate STNs at 1.5 T with minimal image distortion, which reveals variation in STN position and dimensions in the range of nucleus size. This puts under question the rationale of use of standard STN coordinates during DBS surgery.

Landmark‐based software for anatomical measurements: A precision study

The aim of this study was to develop a software program, called Landmarker, which would aid studies of complex anatomical morphometry by simplifying the manual identification of landmarks in 3D images. We also tested its precision on routine magnetic resonance imaging (MRI) scans. To understand human biological variation, there is a need to identify morphological characteristics from the exterior and the interior of human anatomy. MRI, as opposed to other radiographic methods (mainly based on X-ray techniques), supplies good soft tissue contrast, which allows for more complex assessments than what bony landmarks can provide. Because automation of this assessment is highly demanding, one of the primary goals for the new software was to enable more rapid identification of landmark sets in 3D image data. Repeat acquisition of head MRIs having a resolution of 0.94 x 0.94 x 1.20 mm3 were performed on 10 volunteers. Intra- and interoperator, as well as interacquisition variations of manual identification of exterior, craniofacial interior, and brain landmarks were studied. The average distances between landmarks were <1.8 mm, <2.3 mm, and <2.0 mm in the intra- and interoperator, and interacquisition evaluations, respectively. This study presents new software for time efficient identification of complex craniofacial landmarks in 3D MRI. To the best of our knowledge, no evaluation of software for rapid landmark-based analysis of complex anatomies from 3D MR data has yet been presented. This software may also be useful for studies in other anatomical regions and for other types of image data.

NEW SEVERITY INDICES FOR QUANTIFYING SINGLE-SUTURE METOPIC CRANIOSYNOSTOSIS

To describe novel severity indices with which to quantify severity of trigonocephaly malformation in children diagnosed with isolated metopic synostosis. Computed tomographic scans of the cranium were obtained from 38 infants diagnosed with isolated metopic synostosis and 53 age-matched control patients. Volumetric reformations of the cranium were used to trace two-dimensional planes defined by the cranium-base plane and well-defined brain landmarks. For each patient, novel trigonocephaly severity indices (TSI) were computed from outline cranium shapes on each of these planes. The metopic severity index based on measurements of interlandmark distances was also computed and a receiver operating characteristic analysis used to compare the accuracy of classification based on TSIs versus that based on the metopic severity index. The proposed TSIs are a sensitive measure of trigonocephaly malformation that can provide a classification accuracy of 96% with a specificity of 95%, in contrast with 82% of the metopic severity index at the same specificity level. We completed exploratory analysis of outline-based severity measurements computed from computed tomographic image planes of the cranium. These TSIs enable quantitative analysis of cranium features in isolated metopic synostosis that may not be accurately detected by analytic tools derived from a sparse set of traditional interlandmark and semilandmark distances.

Simplified projection of EEG dipole sources onto human brain anatomy

This study was aimed at determining an easy way to project dipole modelling results onto brain anatomy. This simplified projection is based on the estimation of the mean location of the centre of the dipole sphere according to internal brain landmarks. The mean values for the centre location were calculated from ten epileptic patients. To define the axes of the dipole model frame on the patient's magnetic resonance image (MRI), markers were pasted at some electrode positions during the acquisition. An estimation was then made of the mean position of the model centre from the bicommissural line (anterior commissure-posterior commissure [AC-PC]), and a simple transformation to pass from the model cartesian coordinates to the anatomical correlates either in the subject MRI or in the Talairach atlas. These data were then tested in four additional subjects in whom no markers had been placed during the MRI acquisition. On average, the horizontal plane of the sphere model was pitched up 1.9 degrees +/- 1.8 only with respect to the AC-PC horizontal plane, which allowed the projection of dipoles directly onto the Talairach atlas, without pitch. The mean sphere centre was located 7.4 +/- 4.2 mm above the bicommissural line, and 8.2 +/- 1 mm in front of the posterior commissure. In the four additional subjects, projections on MRI and atlas indicated the same anatomical regions and showed high congruence with the physiology or the pathology. This simplified way we report herein has proved to give reliable results. We believe that this method will be useful as a first approximation to project dipole coordinated onto MRI data; moreover, when MRI is unavailable, our results show that dipole modelling results can be superimposed onto atlas slices provided that they are represented according to the AC-PC plane.

Image-guided MR spectroscopy volume of interest localization for longitudinal studies

Longitudinal magnetic resonance spectroscopy (MRS) studies require accurate repositioning of the volume of interest (VOI) over which measurements are made. In this work we present and evaluate a method for the image-guided repositioning of brain volumes of interest. The point-based registration technique we developed allows the repositioning to be performed on-line (i.e. while the patient is in the scanner). MR image volumes were acquired from six subjects, three scans each over the course of a month. During the first scan, two spectroscopy VOIs are visually selected: one in the frontal white matter, the other in the superior cerebellar vermis. The coordinates of 13 internal brain landmarks are also identified. During both subsequent scans, the same 13 landmarks are also identified, and the transformation that registers the first set of landmarks to the subsequent set is computed. This result is used to automatically map the position of the spectroscopy VOIs from the first volume to the current volume. For the six subjects evaluated to date, we show an average repositioning error of the spectroscopy VOIs in the order of 1 mm. This accuracy allows us to conclude that any variations in the MR spectra are unlikely to be due to repositioning error.

Reproducible sampling regimen for specific cortical regions: application to speech-associated areas

The variability in the external gyri pattern of human brains has made the identification of specific cortical areas difficult. Studies correlating cortical structure and function have not consistently controlled for this variability. The aim of the present study was to develop a reliable and reproducible regimen for sampling five speech-associated and one non-speech associated cortical region in the human brain. The gyri of interest were labelled using non-aqueous dye prior to coronal slicing of brains at 3 mm intervals. Using the labelled gyri, a set of internal brain landmarks was established to aid in sampling one block of each cortical region of interest. The position of each internal landmark was determined as a percentage of the total brain length and breadth. The variability in the position of each internal landmark was investigated using analysis of variance and found to be consistent in three dimensions in all cases. The correlation of the sampled cortical region to the internal landmark was consistent in different cases with point to point agreement of 100%. This contrasts with the variability between cases in external gyri features. The sampled region was tested to determine cytoarchitectural variability by measuring the depth of each cortical layer. This technique found that the same cytoarchitectural regions were sampled in each case. As expected, these regions were distinguishable by the significant difference in the depth of different cortical layers. Accurate identification of both the external gyri and internal landmarks occurred with interrater point to point agreement of 90–100%.

STEREOTACTIC SURGICAL SYSTEM CONTROLLED BY COMPUTED TOMOGRAPHY

The three-dimensional data obtained by computed tomographic (CT) scanning offer an advantage in using this imaging technique for stereotactic surgical procedures. This requires interfacing of CT image data with a stereotactic guide. In the performance of functional procedures where the surgical target must be identified from brain landmarks, such as the anterior and posterior commissures, an image reconstruction technique that presents in an image high spatial resolution structural information must be used. The description of a fully hardware- and software-interfaced CT-directed stereotactic surgical system is presented. The logic of operation and examples of images reconstructed with a high spatial resolution algorithm are illustrated. The experimentally determined measurement of an electrode tip localization with this system is within 1 pixel or +/- 0.5 mm in any direction.

Stereotactic surgical system controlled by computed tomography.

The three-dimensional data obtained by computed tomographic (CT) scanning offer an advantage in using this imaging technique for stereotactic surgical procedures. This requires interfacing of CT image data with a stereotactic guide. In the performance of functional procedures where the surgical target must be identified from brain landmarks, such as the anterior and posterior commissures, an image reconstruction technique that presents in an image high spatial resolution structural information must be used. The description of a fully hardware- and software-interfaced CT-directed stereotactic surgical system is presented. The logic of operation and examples of images reconstructed with a high spatial resolution algorithm are illustrated. The experimentally determined measurement of an electrode tip localization with this system is within 1 pixel or +/- 0.5 mm in any direction.

Ultrasonic Modification of Human Brain Structures for Treatment of Neurological Disorders

The methodology of preparation and irradiation by focused ultrasound of brain structures in human patients to favorably modify symptoms of various neurological disorders will be described. This includes the method of brain landmarks location and subsequent geometric positioning of the focus of the ultrasonic beam in arrays of sites in specific structures. The determination of values for the irradiation parameters appropriate for producing selective changes in the tissue components, including the control of auxiliary physical variables which specify the state of the tissue during exposure, will be discussed. Design characteristics of the irradiation, calibration, positioning, and control instrumentation necessary to achieve optimum effects at the present time will be outlined. The techniques and results of irradiation will be illustrated by a motion picture showing human patients undergoing treatment. The modification of abnormal involuntary movements during successive ultrasonic treatment sequences in individuals suffering from Parkinsonism and dystonia musculorum deformans will constitute the clinical material of the motion picture.