Computer-assisted Three-dimensional Reconstruction Research Articles

Multidimensional Mass Spectrometry Assisted Metallo-Supramolecular Chemistry

Multidimensional Mass Spectrometry Assisted Metallo-Supramolecular Chemistry

Long bone fracture reduction and deformity correction using the hexapod external fixator with a new method: a feasible study and preliminary results

BackgroundThe hexapod external fixator (HEF), such as the Taylor spatial frame (TSF), offering the ability of multidirectional deformities correction without changing the structure, whereas there are so many parameters for surgeons to measure and subjective errors will occur inevitably. The purpose of this study was to evaluate the effectiveness of a new method based on computer-assisted three-dimensional (3D) reconstruction and hexapod external fixator for long bone fracture reduction and deformity correction without calculating the parameters needed by the traditional usage.MethodsThis retrospective study consists of 25 patients with high-energy tibial diaphyseal fractures treated by the HEF at our institution from January 2016 to June 2018, including 22 males and 3 females with a mean age of 42 years (range 14–63 years). Hexapod external fixator treatments were conducted to manage the multiplanar posttraumatic deformities with/without poor soft-tissue that were not suitable for internal fixation. Computer-assisted 3D reconstruction and trajectory planning of the reduction by Mimics were applied to perform virtual fracture reduction and deformity correction. The electronic prescription derived from the length changes of the six struts were calculated by SolidWorks. Fracture reduction was conducted by adjusting the lengths of the six struts according to the electronic prescription. Effectiveness was evaluated by the standard anteroposterior (AP) and lateral X-rays after reduction.ResultsAll patients acquired excellent functional reduction and achieved bone union in our study. After correction, the mean translation (1.0 ± 1.1 mm) and angulation (0.8 ± 1.2°) on the coronal plane, mean translation (0.8 ± 1.0 mm) and angulation (0.3 ± 0.8°) on the sagittal plane were all less than those (6.1 ± 4.9 mm, 5.2 ± 3.2°, 4.2 ± 3.5 mm, 4.0 ± 2.5°) before correction (P < 0.05).ConclusionsThe computer-assisted three-dimensional reconstruction and hexapod external fixator-based method allows surgeons to conduct long bone fracture reduction and deformity correction without calculating the parameters needed by the traditional usage. This method is suggested to apply in those unusually complex cases with extensive soft tissue damage and where internal fixation is impossible or inadvisable.

Morphology of the anterolateral ligament: a complex of fibrous tissues spread to the anterolateral aspect of the knee joint

The anterolateral ligament (ALL) has recently received considerable attention as a key structure maintaining the rotational stability of the tibia. However, the morphology of the ALL, particularly the proximal attachment, is controversial. This study aimed to elucidate the morphological relationship between the ALL and its adjacent structures. A total of 25 knees from 22 cadavers were used in the current study. One knee was set at 30°, 60° and 90° of flexion. Stretched or winkled fibrous tissues were then observed with internal and external rotations of the tibia at each angle. In 22 knees, fibrous tissues that were attached to the lateroposterior area to the Gerdy’s tubercle were macroscopically observed. In the other 2 knees, the fibrous tissues were histologically investigated and analyzed using computer-assisted three-dimensional reconstruction. A taut fibrous tissue was observed between the lateroposterior area to the Gerdy’s tubercle and the posterosuperior area to the lateral epicondyle during an internal rotation of the tibia. A complex of fibrous tissues that were attached to the lateroposterior area to the Gerdy’s tubercle spread to the anterolateral aspect of the knee as a sheet-like structure. This complex tissue was composed of the fascia lata and fibrous tissues continuous from the fabellofibular ligament, intermuscular septum, and tendon of the gastrocnemius. Three-dimensional reconstruction showed that each fibrous tissue formed a sheet. The structure recognized as the ALL could not be detected; therefore, the ALL that has been reported to date is considered to be a complex of fibrous tissues with a sheet-like structure.

Three-Dimensional Study of the Terminal Portion in Sprague-Dawley Rat Ejaculatory Ducts.

In mammals, a pair of ejaculatory ducts exists in the urethra at the seminal colliculus. The detailed anatomical structures of the distal end of the ejaculatory ducts of Sprague-Dawley rats were investigated by the computer-assisted three-dimensional reconstruction analysis using light-microscopic serial sections. A three-dimensional reconstruction revealed that in adult rats, the ejaculatory sinus pair consists of two parts: the cranial section - a compartment region composed of a fusion of the ampullary gland duct and the seminal vesicle duct, and the caudal section - a grooved region composed of a long slitlike ejaculatory ostium that extends into the urethra on both sides of the seminal colliculus. But the sphincter structure was not observed. The long axis of the compartment region was approximately 58μm in length, and that of the groove region was approximately 495μm. Although many epithelial glands ducts were distributed throughout the ejaculatory sinuses, the prostate and coagulation gland ducts did not open in these sinuses. The urethra was composed of transitional epithelium, while the ejaculatory sinuses were composed of single to stratified cuboidal epithelium. The ejaculatory ducts continued to the ejaculatory ostium in male adult Sprague-Dawley rat were composed of the seminal vesicle ducts received the ampullary gland ducts.

Computer-assisted three-dimensional reconstruction of the fetal pancreas including the supplying arteries according to immunohistochemistry of pancreatic polypeptide

PurposeComputer-assisted three-dimensional reconstruction of the fetal human pancreas was prepared to reconsider topographical relation between the dorsal/ventral anlagen and the vascular supply.MethodsTissue sections from the upper abdominal viscera of three fetuses were examined. Sections were immunohistochemically stained to determine pancreatic polypeptide expression, a marker of the ventral pancreas.ResultsThe immunohistochemical findings were used to create three-dimensional computer-assisted reconstructions to identify pancreatic arteries. The narrowest part of the pancreas, or the neck, corresponding to a part of the dorsal pancreas, was located on the left side of the common bile duct, portal vein and gastroduodenal artery (GDA). The posterior arterial arcade accompanied the ventral pancreas, whereas the anterior arcade did not. In contrast to the GDA, the splenic artery was clearly separated from the neck in fetuses. The GDA appears to be the primary and stable arterial supply for the neck of the pancreas.ConclusionsThis observation may have implications for the preservation of the neck with the GDA during pancreaticoduodenectomy for benign and low-grade malignant diseases.

Electron microscope tomography: further demonstration of nanocontacts between caveolae and smooth muscle sarcoplasmic reticulum

A spatial relationship between caveolae and sarcoplasmic reticulum (SR) in smooth muscle cells (SMC) was previously reported in computer-assisted three-dimensional reconstruction from transmission electron microscope serial sections. The knowledge of the three-dimensional organization of the cortical space of SMC is essential to understand caveolae function at the cellular level. Cellular tomography using transmission electron microscopy tomography (EMT) is the only available technology to reliably chart the inside of a cell and is therefore an essential technology in the study of organellar nanospatial relationships. Using EMT we further demonstrate here that caveolae and peripheral SR in visceral SMC build constantly spatial units, presumably responsible for a vectorial control of free Ca2+ cytoplasmic concentrations in definite nanospaces.

Structural Determinants of Transmission at Large Hippocampal Mossy Fiber Synapses

Synapses are the key elements for signal processing and plasticity in the brain. To determine the structural factors underlying the unique functional properties of the hippocampal mossy fiber synapse, the complete quantitative geometry was investigated, using electron microscopy of serial ultrathin sections followed by computer-assisted three-dimensional reconstruction. In particular, parameters relevant for transmitter release and synaptic plasticity were examined. Two membrane specializations were found: active zones (AZs), transmitter release sites, and puncta adherentia, putative adhesion complexes. Individual boutons had, on average, 25 AZs (range, 7-45) that varied in shape and size (mean, 0.1 microm2; range, 0.07-0.17 microm2). The mean distance between individual AZs was 0.45 microm. Mossy fiber boutons and their target structures were mostly ensheathed by astrocytes, but fine glial processes never reached the active zones. Two structural factors are likely to promote synaptic cross talk: the short distance between AZs and the absence of fine glial processes at AZs. Thus, synaptic cross talk may contribute to the efficacy of hippocampal mossy fiber synapses. On average, a bouton contained 20,400 synaptic vesicles; approximately 900 vesicles were located within 60 nm from the active zone, approximately 4400 between 60 and 200 nm, and the remaining beyond 200 nm, suggesting large readily releasable, recycling, and reserve pools. The organization of the different pools may be a key structural correlate of presynaptic plasticity at this synapse. Thus, the mossy fiber bouton differs fundamentally in structure and function from the calyx of Held and other central synapses.

Successes and Rewards in Sharing Digital Reconstructions of Neuronal Morphology

The computer-assisted three-dimensional reconstruction of neuronal morphology is becoming an increasingly popular technique to quantify the arborization patterns of dendrites and axons. The resulting digital files are suitable for comprehensive morphometric analyses as well as for building anatomically realistic compartmental models of membrane biophysics and neuronal electrophysiology. The digital tracings acquired in a lab for a specific purpose can be often re-used by a different research group to address a completely unrelated scientific question, if the original investigators are willing to share the data. Since reconstructing neuronal morphology is a labor-intensive process, data sharing and re-analysis is particularly advantageous for the neuroscience and biomedical communities. Here we present numerous cases of "success stories" in which digital reconstructions of neuronal morphology were shared and re-used, leading to additional, independent discoveries and publications, and thus amplifying the impact of the "source" study for which the data set was first collected. In particular, we overview four main applications of this kind of data: comparative morphometric analyses, statistical estimation of potential synaptic connectivity, morphologically accurate electrophysiological simulations, and computational models of neuronal shape and development.

The morphology of excitatory central synapses: from structure to function

Synapses are the key elements for signal transduction and plasticity in the brain. For a better understanding of the functional signal cascades underlying synaptic transmission, a quantitative morphological analysis of the pre- and postsynaptic structures that represent morphological correlates for synaptic transmission is important. In particular, realistic values of the number, distribution, and geometry of synaptic contacts and the organization of the pool of synaptic vesicles provide important constraints for realistic models and numerical simulations of those parameters of synaptic transmission that, at present, are still not accessible to experiment. Although all synapses are composed of almost the same structural elements, the composition of these elements within a given synapse and the microcircuit in which they are embedded are the deciding factors determining its function. One possible way to analyze these structures is by computer-assisted three-dimensional reconstructions of synapses and their subsequent quantitative analysis based on ultrathin serial sections. The present review summarizes and discusses the morphology of five central excitatory synapses that are quantitatively well described: (1) a giant synapse, the so-called Calyx of Held, in the medial nucleus of the trapezoid body in the auditory brain stem, (2) the mossy fiber terminal establishing synapses with multiple cerebellar granule cell dendrites, (3) the mossy fiber bouton in the hippocampus predominantly terminating on proximal dendrites of CA3 pyramidal neurons, (4) the climbing fiber-Purkinje cell synapse in the cerebellum, and (5) cortical input synapses on the basal dendrites of layer 5 pyramidal cells. The detailed morphological description of these synaptic structures may help to define the morphological correlates of the functional parameters of synaptic transmission, such as the readily releasable pool of synaptic vesicles, of release, and of the variability of quantal size and might therefore explain the existing differences in the function between individual synapses embedded in different microcircuits.

Loss of PECAM-1 Function Impairs Alveolarization

The final stage of lung development in humans and rodents occurs principally after birth and involves the partitioning of the large primary saccules into smaller air spaces by the inward protrusion of septae derived from the walls of the saccules. Several observations in animal models implicate angiogenesis as critical to this process of alveolarization, but all anti-angiogenic treatments examined to date have resulted in endothelial cell (EC) death. We therefore targeted the function of platelet endothelial cell adhesion molecule, (PECAM-1), an EC surface molecule that promotes EC migration and has been implicated in in vivo angiogenesis. Administration of an anti-PECAM-1 antibody that inhibits EC migration, but not proliferation or survival in vitro, disrupted normal alveolar septation in neonatal rat pups without reducing EC content. Three-dimensional reconstruction of lungs showed that pups treated with a blocking PECAM-1 antibody had remodeling of more proximal branches resulting in large tubular airways. Subsequent studies in PECAM-1-null mice confirmed that the absence of PECAM-1 impaired murine alveolarization, without affecting EC content, proliferation, or survival. Further, cell migration was reduced in lung endothelial cells isolated from these mice. These data suggest that the loss of PECAM-1 function compromises postnatal lung development and provide evidence that inhibition of EC function, in contrast to a loss of viable EC, inhibits alveolarization.

Deletion of Highly Conserved Arginine-Rich RNA Binding Motif in Cowpea Chlorotic Mottle Virus Capsid Protein Results in Virion Structural Alterations and RNA Packaging Constraints

The N-proximal region of cowpea chlorotic mottle virus (CCMV) capsid protein (CP) contains an arginine-rich RNA binding motif (ARM) that is also found in the CPs of other members of Bromoviridae and in other RNA binding proteins such as the Tat and Rev proteins of human immunodeficiency virus. To assess the critical role played by this motif during encapsidation, a variant of CCMV RNA3 (C3) precisely lacking the ARM region (C3/Delta919) of its CP gene was constructed. The biology and the competence of the matured CP derived in vivo from C3/Delta919 to assemble and package progeny RNA was examined in whole plants. Image analysis and computer-assisted three-dimensional reconstruction of wild-type and mutant virions revealed that the CP subunits bearing the engineered deletion assembled into polymorphic virions with altered surface topology. Northern blot analysis of virion RNA from mutant progeny demonstrated that the engineered mutation down-regulated packaging of all four viral RNAs; however, the packaging effect was more pronounced on genomic RNA1 and RNA2 than genomic RNA3 and its CP mRNA. In vitro assembly assays with mutant CP subunits and RNA transcripts demonstrated that the mutant CP is inherently not defective in packaging genomic RNA1 (53%) and RNA2 (54%), but their incorporation into virions was competitively inhibited by the presence of other viral RNAs. Northern blot analysis of RNA encapsidation in vivo of two distinct bromovirus RNA3 chimeras, constructed by exchanging CPs having the Delta919 deletion, demonstrated that the role of the conserved N-terminal ARM in recognizing and packaging specific RNA is distinct for each virus.

Cell biology of mating in Candida albicans.

It was recently demonstrated that strains homozygous for either of the mating type-like loci MTLa and MTLalpha of Candida albicans undergo white-opaque switching and that expression of the opaque-phase phenotype greatly enhances mating between strains. Exploiting the latter property to obtain high-frequency mating, we have characterized the cell biology of the mating process of C. albicans. Employing continuous videomicroscopy, computer-assisted three-dimensional reconstruction of living cells, and fluorescence microscopy, we have monitored the mating-associated processes of conjugation, tube formation, fusion, budding, septum formation, and daughter cell development and the spatial and temporal dynamics of nuclear migration and division. From these observations, a model for the stages in C. albicans mating is formulated. The stages include shmooing, chemotropism of conjugation tubes, fusion of tubes and nuclear association, vacuole expansion and nuclear separation in the conjugation bridge, asynchronous nuclear division in the zygote, bud growth, nuclear migration into the daughter cell, septation, and daughter cell budding. Since there was no cytological indication of karyogamy, genetic experiments were performed to assess marker segregation. Recombination was not observed, suggesting that mating takes place in the absence of karyogamy between naturally occurring, homozygous a and alpha strains. This study provides the first description of the cell biology of the mating process of C. albicans.

Ultrastructural studies define soluble macromolecular, particulate, and cellular transendothelial cell pathways in venules, lymphatic vessels, and tumor-associated microvessels in man and animals.

We present de novo studies and review published efforts from our laboratory, spanning 12 years (from 1988 to 2000), where we have used ultrastructural approaches to study the functional anatomy of the microvasculature in man and animals in health and disease. These efforts have defined a new endothelial cell organelle, termed the vesiculo-vacuolar organelle (VVO), which participates in the regulated transendothelial cell passage of soluble macromolecules. The studies defining this organelle utilized ultrathin serial sections, three-dimensional computer-assisted reconstructions, and ultrastructural electron-dense tracers to establish luminal to abluminal transendothelial cell continuity of VVOs. Commonality of VVOs and caveolae is suggested by the ultrastructural anatomy of individual units of VVOs and caveolae, the presence of caveolin in both structures, and a mathematical analysis of morphometric data, all of which suggest that VVOs form from fusions of individual size units equivalent to vesicles of caveolar size. Ultrastructural studies have localized potent permeability factors and their specific receptors to VVOs in in vivo tumor and allergic inflammation models. Regulation of permeability through VVOs has been quantified and shown to be increased in tumor microvessels and in control vessels exposed to potent permeability-inducing mediators. The transendothelial cell passage of particulate macromolecules occurs by vacuolar transport in tumor vessels; in permeability factor-exposed control vessels, colloidal carbon traversed endothelial cells via the development of pores that did not communicate with or disrupt intercellular junctions by gap formation. Serial section and computer-assisted reconstructions established these findings and suggested the possible development of transendothelial cell pores from VVOs. Serial sectioning and computer-assisted three-dimensional reconstructions of ultrastructural samples of an acute inflammation model revealed a transendothelial cell traffic route for motile neutrophils and platelets in the absence of classical ultrastructural criteria for regulated secretion from either cell.

Apoptosis in regressive deciduous tooth germs of Suncusmurinus evaluated by the the TUNEL method and electron microscopy

Apoptosis in regressive primary (deciduous) dental primordia was examined in the embryos of Suncus murinus, which is a monophyodont. The primary tooth germs of S. murinus are temporarily formed and disappear during the embryonic period before they are calcified. Most primary tooth germs reach the bell stage and degenerate by embryonic day 22 (E22). Light microscopy on haematoxylin–eosin-stained sections revealed that intensely labelled granular substances are frequently present in the epithelial portion (enamel organs) of the deciduous tooth germs during the period from E18 to E20. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate–biotin nick end labelling method, computer-assisted three-dimensional reconstructions, and electron microscopy confirmed that these variable-sized granular substances are similar to apoptotic cells or bodies. Apoptotic structures were mainly found in the primary tooth germ located on the buccal surface of the secondary (successional) tooth germ. These results lead to the conclusion that apoptosis is closely associated with the involution and disappearance of the deciduous tooth germ in S. murinus. A primary tooth germ was observed on the buccal side of all the corresponding successional tooth germs, although the buccal surface of the secondary tooth germ of third upper molar teeth developed only to epithelial thickening without mesenchymal condensation. The findings, therefore, suggest that apoptosis is responsible for disappearance of the primary dental primordia during tooth development in S. murinus.

Distribution and volumetric assessment of initial approximal caries lesions in human premolars and permanent molars using computer-aided three-dimensional reconstruction

Serial sections from 21 extracted premolars and permanent molars, divided into three age groups (group 1, 10–19 years; group 2, 20–39 years; group 3, 50–69 years.), were viewed by polarized light microscopy for reconstruction of the caries lesions. The volumes of the lesional body and the transparent zone, and the volumes of early dentinal lesions were calculated; and an enamel demineralization index (EDI) and an enamel–dentine demineralization index (EDDI), representing the volumetric ratio of the body of the lesion to the translucent zone, and the body of the lesion to the volume of the early dentinal lesion, respectively, were determined. The method showed that there are three typical sites of individual initial caries lesions at the approximal surface: within the contact area, in the subcontact area, and in the cervical area. Volumetric assessment demonstrated a larger volume of the body of the lesion in older teeth with a smaller volume of the translucent zone relative to the lesional body. From these results it can be concluded that there are usually more than one individual initial caries lesions at the approximal tooth surface. Calculation of demineralization indices demonstrated different features for small lesions with pronounced transparent zones and for large lesions with small transparent zones. The computer-assisted three-dimensional reconstruction technique and the volumetric assessment are of value in investigations of the micromorphology and progression of natural caries lesions in permanent teeth.

Morphology of the human atrioventricular node is age dependent: a feature of potential clinical significance.

Advances in catheter ablation procedures have created the need to understand better the morphology of the AV node (AVN), particularly as it relates to age. This study was based on 40 normally structured hearts obtained at autopsy from patients without a history of tachyarrhythmia in the following age ranges: < 1 year (n = 19); 1-12 years (n = 11); and 12-20 years (n = 10). In 38 hearts, the AV septal junctional area was removed en bloc and serially sectioned at 10-microm thickness at right angles to the AV annulus. The length of the compact node and the rightward and leftward inferior extensions were calculated. Computer-assisted three-dimensional reconstructions were made of six hearts. The ratio of right extension to compact AVN showed a statistically significant increase with age; the increase in ratio of left extension to compact AVN was not statistically significant. In addition, with increasing age the geometry of the AVN changed from a half-oval to a spindle shape, concomitant with development of a distinct so-called muscular AV septum. The three-dimensional reconstructions showed widening of the transitional cell zone with an increase in fibrofatty tissue related to age. The AVN, inferior extensions, and transitional cell zone show distinct age-related changes that may be clinically relevant. The increase in length of the inferior extensions may set the scene for AVN reentry and could explain why this condition is more frequent in young adults than in infants.

The Quantitative Detection of Posttraumatic Osteoarthrosis after Fractures of the Tibial Plateau Using MRI-based Chondrovolumetry

Despite developing better treatment for fractures of the tibial head, particularly intraarticular ones, late degenerative arthritis still presents a very serious problem. Difficulties in the diagnosis of early secondary degenerative changes derive from the fact that plain radiographs are limited to the detection of late manifestations and indirect signs of osteoarthritis because articular cartilage is not visible radiographically. To examine the extent of secondary arthrosis after intraarticular fracture and surgical treatment of the tibial head, we reviewed 25 patients for an objective quantitative measurement of the hyaline cartilage volume of the injured knee. Using magnetic resonance imaging and computer-assisted three-dimensional reconstruction, these MRI-based chondrovolumetric measurements were compared with the hyaline cartilage volume of the uninjured knee of the same patient. We discovered a highly significant reduction (p < 0.001) of the hyaline cartilage volume at the tibial plateau of the injured side. Additionally, there was not only a significant decrease of the joint cartilage at the tibial plateau but also of the cartilage volume of the patella (p = 0.001) and of the femur (p = 0.007) at the injured knee. None of the reviewed patients showed equal or more cartilage volume at the tibial plateau of the injured knee compared to the uninjured side. Our findings indicate that every intraarticular fracture leads more or less to secondary posttraumatic osteoarthrosis. MRI-based chondrovolumetry provides a promising new method for detecting and monitoring articular cartilage leasions and for evaluating various kinds of chondroprotective treatment, such as osteochondral grafting, drugs, physiotherapy, and correction osteotomy.

Modeling prostate cancer distributions

Objectives. To use computer-assisted three-dimensional (3D) reconstruction to study cancer distribution in the prostate. The distributions have been determined using data from 81 prostates surgically removed because of cancer. Methods. The pattern of distribution was determined by reshaping (morphing) all prostates in the same size category (small, medium, large) into the same shape and by overlayering the 3D distribution of all cancers into a “unit prostate.” Also, the pattern of 3D distribution was defined for small, medium, and large volume cancers. Results. The study yielded a clear, visual “scatter diagram” representation of the statistics of prostate cancer distribution. It confirmed previous general knowledge: small cancers are mainly found in the lower one third and principally in the dorsolateral part of the gland. Conclusions. This report is part of the investigations preliminary to establishing an optimal protocol for needle biopsy of prostate cancer.

Localization of hand motor activation in Broca's pli de passage moyen.

The object of this study was to identify a reliable surface landmark for the hand motor area and to demonstrate that it corresponds to a specific structural component of the precentral gyrus. Positron emission tomography (PET) activation studies for hand motor function were reviewed in 12 patients in whom magnetic resonance imaging results were normal. Each patient performed a hand opening and closing task. Using a computer-assisted three-dimensional reconstruction of the surface of each hemisphere studied, the relationship of the hand motor area with cortical surface landmarks was evaluated. The region of hand motor activation can be reliably identified on the surface of the brain by assessing anatomical relationships to nearby structures. After identification of the central sulcus, the superior and middle frontal gyrus can be seen to arise from the precentral gyrus at a perpendicular angle. A bend or genu in the precentral gyrus is constantly seen between the superior and middle frontal gyrus, which points posteriorly (posteriorly convex). The location of hand motor function, identified using PET activation studies, is within the central sulcus at the apex of this posteriorly pointing genu. The apex of the genu of the precentral gyrus leads to a deep cortical fold connecting the pre- and postcentral gyri and elevating the floor of the central sulcus. This deep fold was described by Paul Broca as the pli de passage fronto-parietal moyen, and the precentral bank of the pli de passage represents the anatomical substratum of hand motor function. Observers blinded to the results of the activation studies were able to identify the hand motor area reliably after instruction in using these surface landmarks.

Localization of hand motor activation in Broca's pli de passage moyen

Object The object of this study was to identify a reliable surface landmark for the hand motor area and to demonstrate that it corresponds to a specific structural component of the precentral gyrus. Methods Positron emission tomography (PET) activation studies for hand motor function were reviewed in 12 patients in whom magnetic resonance imaging results were normal. Each patient performed a hand opening and closing task. Using a computer-assisted three-dimensional reconstruction of the surface of each hemisphere studied, the relationship of the hand motor area to cortical surface landmarks was evaluated. Conclusions The region of hand motor activation can be reliably identified on the surface of the brain by assessing anatomical relationships to nearby structures. After identification of the central sulcus, the superior and middle frontal gyrus can be seen to arise from the precentral gyrus at a perpendicular angle. A bend or genu in the precentral gyrus is constantly seen between the superior and middle frontal gyrus, which points posteriorly (posteriorly convex). The location of hand motor function, identified using PET activation studies, is within the central sulcus at the apex of this posteriorly pointing genu. The apex of the genu of the precentral gyrus leads to a deep cortical fold connecting the pre- and postcentral gyri and elevating the floor of the central sulcus. This deep fold was described by Paul Broca as the pli de passage fronto-pariétal moyen, and the precentral bank of the pli de passage represents the anatomical substratum of hand motor function. Observers blinded to the results of the activation studies were able to identify the hand motor area reliably after instruction in using these surface landmarks.