Increased representation of the non-dominant hand in pianists demonstrated by measurement of 3D morphology of the central sulcus.

Background: Post-mortem and magnetic resonance imaging (MRI) studies of the central sulcus, as an indicator of motor cortex, have shown that in the general population there is greater representation of the dominant compared to the non-dominant hand. Studies of musicians, who are highly skilled in performing complex finger movements, have suggested this dominance is affected by musical training, but methods and findings have been mixed. Objective: In the present study, an automated image analysis pipeline using a 3D mesh approach was applied to measure central sulcus (CS) asymmetry on MR images obtained for a cohort of right-handed pianists and matched controls. Methods: The depth, length, and surface area (SA) of the CS and thickness of the cortical mantle adjacent to the CS were measured in each cerebral hemisphere by applying the BrainVISA Morphologist 2012 software pipeline to 3D T1-weighted MR images of the brain obtained for 15 right-handed pianists and 14 controls, matched with respect to age, sex, and handedness. Asymmetry indices (AIs) were calculated for each parameter and multivariate analysis of covariance (MANCOVA), and post hoc tests were performed to compare differences between the pianist and control groups. Results: A one-way MANCOVA across the four AIs, controlling for age and sex, revealed a significant main effect of group (P = 0.04), and post hoc analysis revealed that while SA was significantly greater in the left than the right cerebral hemisphere in controls (P < 0.001), there was no significant difference between left and right SA in the pianists (P = 0.634). Independent samples t-tests revealed that the SA of right CS was significantly larger in pianists compared to controls (P = 0.015), with no between-group differences in left CS. Conclusions: Application of an image analysis pipeline to 3D MR images has provided robust evidence of significantly increased representation of the non-dominant hand in the brain of pianists compared to age-, sex-, and handedness-matched controls. This finding supports prior research showing structural differences in the central sulcus in musicians and is interpreted to reflect the long-term motor training and high skill level of right-handed pianists in using their left hand.

Measurement of Sylvian Fissure asymmetry and occipital bending in humans and Pan troglodytes.

The evolution of human-specific lateralised functions such as language has been linked to the development of structural asymmetries in the brain. Here we applied state of the art image analysis techniques to measure Sylvian Fissure (SF) asymmetry and Occipital Bending (OB) in 3D Magnetic Resonance (MR) images of the brain obtained in-vivo for 30 humans and 30 chimpanzees (Pan troglodytes). SF morphology differed between species, with the human SF terminating more superiorly in right inferior parietal lobe, an asymmetry that was on average absent in chimpanzees (F (1,52) = 5.963, p = 0.018). Irrespective of morphology, Total SF Length was, as previously reported, leftward in humans but not in chimpanzees, although the difference did not reach significance between species. However, when only brains possessing comparable bilateral SF bifurcation morphology were compared, humans showed previously reported "Typical" left-lateralised Anterior-Horizontal (AH-SF) and right-lateralised Vertical (V-SF) SF asymmetries. In contrast, chimpanzees lacked both asymmetries, and this approached being a significant difference between-species in the AH-SF segment (F (1, 34) = 3.680, p = 0.064). On average in humans the left occipital lobe crossed the midline toward the right (Rightward OB) which was significantly different from the chimpanzee cohort that showed no average OB (Independent-Samples Mann-Whitney U Test, p = 0.012). Furthermore, OB was related to SF asymmetry in humans, such that the more rightward V-SF and leftward AH-SF, the more rightward the OB. This "Default" pattern of SF and OB asymmetries was found in 41.7% of human individuals with bilateral SF bifurcation but none of the chimpanzees. To our knowledge, this is the first study highlighting that a pattern of SF and OB asymmetry distinguishes the human from the chimpanzee brain, and suggests this may be associated with a unique trajectory of brain development and functional abilities in humans.

Brain structural and functional asymmetry in human situs inversus totalis.

Magnetic resonance imaging was used to investigate brain structural and functional asymmetries in 15 participants with complete visceral reversal (situs inversus totalis, SIT). Language-related brain structural and functional lateralization of SIT participants, including peri-Sylvian gray and white matter asymmetries and hemispheric language dominance, was similar to those of 15 control participants individually matched for sex, age, education, and handedness. In contrast, the SIT cohort showed reversal of the brain (Yakovlevian) torque (occipital petalia and occipital bending) compared to the control group. Secondary findings suggested different asymmetry patterns between SIT participants with (n = 6) or without (n = 9) primary ciliary dyskinesia (PCD, also known as Kartagener syndrome) although the small sample sizes warrant cautious interpretation. In particular, reversed brain torque was mainly due to the subgroup with PCD-unrelated SIT and this group also included 55% left handers, a ratio close to a random allocation of handedness. We conclude that complete visceral reversal has no effect on the lateralization of brain structural and functional asymmetries associated with language, but seems to reverse the typical direction of the brain torque in particular in participants that have SIT unrelated to PCD. The observed differences in asymmetry patterns of SIT groups with and without PCD seem to suggest that symmetry breaking of visceral laterality, brain torque, and language dominance rely on different mechanisms.

Spinal intradural, extramedullary anaplastic ependymoma with an extradural component: Case report and review of the literature.

BACKGROUND: There have been 18 reported cases of primary spinal intradural, extramedullary ependymomas reported in the literature. One of the 18 cases had an extradural component and was benign. Our case is the second spinal intradural, extramedullary ependymoma with an extradural component and the first with its initial presentation as an anaplastic ependymoma. CASE DESCRIPTION: A 50-year-old male presented with bilateral upper thigh weakness and thoracic numbness. His exam showed the pin-prick level at T5. Magnetic resonance imaging (MRI) of the thoracic spine showed an enhancing lesion at T5-6 with severe compression of the spinal cord with a dumbbell shape extension of the tumor through the right T5-6 neural foramen. The patient had a laminectomy at T4-T6 with the resection of the tumor. Postoperatively, the patient regained full strength in his lower extremities. Intraoperatively, the tumor was found to be intradural, extramedullary with an extradural component. The tumor was found to be an anaplastic ependymoma. CONCLUSIONS: Even though spinal intradural extramedullary ependymomas are very rare, surgeons must be aware that on MRI, they can be mistaken for meningiomas or nerve sheath tumors especially if there is an extradural component. Our case report is the first intradural, extramedullary ependymoma that is anaplastic and has an extradural component. A review of the literature provides little information on the treatment and prognosis for these tumors especially if they are anaplastic. We propose that the treatment, as done in our case, should be complete resection of the tumor with spinal radiotherapy to the tumor level.

Firefly luciferase-based dynamic bioluminescence imaging: a noninvasive technique to assess tumor angiogenesis.

OBJECTIVE: Bioluminescence imaging (BLI) is emerging as a cost-effective, high-throughput, noninvasive, and sensitive imaging modality to monitor cell growth and trafficking. We describe the use of dynamic BLI as a noninvasive method of assessing vessel permeability during brain tumor growth. METHODS: With the use of stereotactic technique, 10 firefly luciferase-transfected GL26 mouse glioblastoma multiforme cells were injected into the brains of C57BL/6 mice (n = 80). After intraperitoneal injection of D-luciferin (150 mg/kg), serial dynamic BLI was performed at 1-minute intervals (30 seconds exposure) every 2 to 3 days until death of the animals. The maximum intensity was used as an indirect measurement of tumor growth. The adjusted slope of initial intensity (I90/Im) was used as a proxy to monitor the flow rate of blood into the vascular tree. Using a modified Evans blue perfusion protocol, we calculated the relative permeability of the vascular tree at various time points. RESULTS: Daily maximum intensity correlated strongly with tumor volume. At postinjection day 23, histology and BLI demonstrated an exponential growth of the tumor mass. Slopes were calculated to reflect the flow in the vessels feeding the tumor (adjusted slope = I90/Im). The increase in BLI intensity was correlated with a decrease in adjusted slope, reflecting a decrease in the rate of blood flow as tumor volume increased (y = 93.8e-0.49, R2 = 0.63). Examination of calculated slopes revealed a peak in permeability around postinjection day 20 (n = 42, P < .02 by 1-way analysis of variance) and showed a downward trend in relation to both postinjection day and maximum intensity observed; as angiogenesis progressed, tumor vessel caliber increased dramatically, resulting in sluggish but increased flow. This trend was correlated with Evans blue histology, revealing an increase in Evans blue dye uptake into the tumor, as slope calculated by BLI increases. CONCLUSION: Dynamic BLI is a practical, noninvasive technique that can semiquantitatively monitor changes in vascular permeability and therefore facilitate the study of tumor angiogenesis in animal models of disease.

Resolution of syringomyelia after release of tethered cord.

BACKGROUND: Syringomyelia is an abnormal cystic dilatation of the spinal cord caused by excessive accumulation of CSF. Patients can develop various neurologic deficits secondary to untreated syringomyelia, some of which can be permanent despite surgical intervention. CASE DESCRIPTION: The authors present a patient with syringomyelia, aortic coarctation, and tethered cord syndrome. Serial radiographic imaging demonstrated initial significant reduction of the thoracic syrinx after coarctation repair and release of tethered cord. However, subsequent follow-up imaging revealed partial recurrence. CONCLUSION: This case provides evidence of a possible cause-effect relationship between syringomyelia and tethered cord. It demonstrates the indication of surveillance imaging of the entire spine to ensure that all potential etiologies of syringomyelia are identified and treated. Furthermore, it illustrates the complex dynamic nature of syrinx physiology and reinforces the importance of serial follow-up studies after surgical intervention.

HMG-CoA reductase inhibition causes increased necrosis and apoptosis in an in vivo mouse glioblastoma multiforme model.

BACKGROUND: Statins are thought to have tumorolytic properties, reducing angiogenesis by inhibiting pro-angiogenic factors and inducing apoptosis of mural pericytes within the tumor vascular tree. MATERIALS AND METHODS: An orthotopic mouse glioblastoma (GL-26) model was used to investigate the effect of simvastatin on glioblastoma vasculature in vivo. GL-26 cells were implanted into the striatum of C5LKa mice treated with either control, low- or high-dose simvastatin. Brains were analyzed for necrotic volume, apoptosis, morphology and pericytic cells within the vascular tree. RESULTS: Low-dose simvastatin increased necrosis and apoptosis compared to both control and high-dose simvastatin groups. High-dose simvastatin increased vessel caliber by reducing pericytic cells along the tumor vessel wall compared to both control and low-dose simvastatin groups. CONCLUSION: Simvastatin has a dual effect on tumorigenesis. At high doses, it may worsen instead of 'normalizing' tumor angio-architecture, albeit low doses affect tumor cell survival by promoting necrosis and apoptosis.

The temporal correlation of dynamic contrast-enhanced magnetic resonance imaging with tumor angiogenesis in a murine glioblastoma model.

OBJECTIVE: Glioblastoma multiforme (GBM) is a WHO grade IV malignant brain tumor with poor prognosis, despite advances in surgical and adjuvant therapy. GBM is characterized by areas of central necrosis and high levels of angiogenesis, during which increased vascular permeability allows for the extravasation of endothelial progenitor cells to support blood vessel and tumor growth. The purpose of this study was to characterize changes in tumor vascular permeability, vascular density and vessel morphology in vivo during angiogenesis. METHODS: An orthotropic murine (GL26) glioblastoma model was used in this study. in vivo serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in combination with histologic and molecular genetic analyses was performed to correlate in vivo imaging of vascular development. RESULTS: DCE-MRI revealed a significant change in tumor vessel permeability dependent upon tumor progression and size. Time to max signal intensity displayed a stepwise increase between days 21 and 24 (p<0.05), a critical period before exponential tumor growth during which a significant increase in tumor vascular density and vessel caliber is observed on histology. Furthermore, quantitative real-time PCR revealed a corollary increase in angiogenic signaling molecules before the observed changes on DCE-MRI. DISCUSSION: In vivo changes of orthotopic glioma blood vessel permeability as shown by DCE-MRI correlates with histologic quantification of vascular density and vessel caliber as well as with the molecular expression of angiogenic factors. DCE-MRI is a useful tool for non-invasive in vivo monitoring of angiogenesis in pre-clinical tumor models.

Congenital glioblastoma multiforme: case report and review of the literature.

Congenital glioblastoma multiforme is a rare primary brain tumor that has a unique biology distinct from pediatric and adult variants. In this report, we present a case of congenital glioblastoma with complicated management course. A literature review of previously reported cases is included to illustrate the epidemiology and natural history of this disease. A 9-month-old male infant developed acute lethargy, hemiparesis and unilaterally dilated pupil. Imaging studies revealed a large hemispheric tumor, resulting in significant midline shift suggestive of impending herniation. Emergent tumor cystic fluid drainage was performed at initial presentation. A frontotemporoparietal craniotomy was performed on the following day to attempt a gross total resection. Adjuvant chemotherapy consisting of oral temozolomide was administered. The patient eventually succumbed 4 months later due to aggressive tumor progression. Congenital glioblastoma should be included in the differential diagnosis of infants with large intracranial tumors. Although surgical intervention may increase survival, the overall outcome remains poor despite maximal multimodal treatment.

The cancer stem cell-vascular niche complex in brain tumor formation.

The cancer stem cell (CSC) theory hypothesizes that a small subpopulation of cells within a tumor mass is responsible for the initiation and maintenance of the tumor. The idea that brain tumors arise from this specific subset of self-renewing, multipotent cells that serve as the locus for tumor formation, has gained great support as evidenced by recent advancements in the biology of breast and colon cancer. It is well established that recruitment of bone marrow-derived proangiogenic progenitor cells and angiogenesis are key events in the process of brain tumor formation; however, the orchestration of these events by the CSC population has only recently been unveiled. In this review, we first introduce the CSC theory and examine the functional development of the vascular niche, its purpose, constituents, and contribution to the development of the CSC-vascular niche complex. Through this discussion, we aim to shed light on the events that may be targeted for therapeutic intervention.

Moyamoya disease in pediatric patients: outcomes of neurosurgical interventions.

Neurosurgical interventions for moyamoya disease (MMD) in pediatric patients include direct, indirect, and combined revascularization procedures. Each technique has shown efficacy in the treatment of pediatric MMD; however, no single study has demonstrated the superiority of one technique over another. In this review, the authors explore the various studies focused on the use of these techniques for MMD in the pediatric population. They summarize the results of each study to clearly depict the clinical outcomes achieved at each institution that had utilized direct, indirect, or combined techniques. In certain studies, multiple techniques were used, and the clinical or radiological outcomes were compared accordingly. Direct techniques have been shown to aid a reduction in perioperative strokes and provide immediate revascularization to ischemic areas; however, these procedures are technically challenging, and not all pediatric patients are appropriate candidates. Indirect techniques have also shown efficacy in the pediatric population but may require a longer period for revascularization to occur and perfusion deficits to be reversed. The authors concluded that the clinical efficacy of one technique over another is still unclear, as most studies have had small populations and the same outcome measures have not been applied. Authors who compared direct and indirect techniques noted approximately equal clinical outcomes with differences in radiological findings. Additional, larger studies are needed to determine the advantages and disadvantages of the different techniques for the pediatric age group.

Hematopoietic stem cell-derived pericytic cells in brain tumor angio-architecture.

Bone marrow-derived cells are recruited into tumor vasculature in response to angiogenic signals, and some of the cells within the newly forming tumor vessels are hematopoietic stem cells (HSCs) in origin. Previous studies suggest that bone marrow-derived pericytes are associated with newly formed vessels in tumors. In this study, we used an orthotopic rat glioma model (RT-2/RAG) to examine the contribution of long-term hematopoietic stem cell (LT-HSC)-derived pericytic cells to brain tumor angiogenesis. Mice (RAG-2/KO5.2) were lethally irradiated, and their hematopoietic cells were repopulated by transplantation of double fluorescence-activated cell-sorted LT-HSCs that express green fluorescent protein (GFP+). RT-2/RAG cells were then injected into the striatum of the chimeric mice 6 weeks post-transplantation. The animals were sacrificed 9 days after tumor implantation, and the incorporation and lineage-specific marker expression profile of the GFP+ cells within the growing tumor and tumor periphery were analyzed. LT-HSC-derived GFP+ cells were noted to incorporate onto the surface of tumor vessels within the perivascular space. LT-HSC-derived GFP+ cells express the pericyte progenitor marker, platelet-derived growth factor receptor-beta (PDGFR beta), as well as mature perictyte markers such as nerve/glial antigen 2 proteoglycan (NG2), alpha-smooth muscle actin (alpha SMA), and desmin. These LT-HSC-derived cells may represent a population of progenitor or committed pericytes within the neovascular tree and may play a role in shaping the angio-architecture in the vascular niche of brain tumors.

Molecular events of brain metastasis.

The brain is a privileged site of systemic cancer metastasis. The stages of the metastatic journey from the periphery to the brain are driven by molecular events that tie the original site of disease to the distant host tissue. This preference is not arbitrary but rather a directed phenomenon that includes such critical steps as angiogenesis and the preparation of the premetastatic niche. It appears that the connection between naive brain and cancer cells is made in advance of any metastatic breach of the blood-brain barrier. This contributes to the preferential homing of cancer cells to the brain. Delineation of the guidance mechanisms and elements that influence cancer cell motility and dormancy are important for the advancement of treatment modalities aimed at the remediation of this devastating disease.

Multimodality molecular imaging of glioblastoma growth inhibition with vasculature-targeting fusion toxin VEGF121/rGel.

UNLABELLED: Vascular endothelial growth factor A (VEGF-A) and its receptors, Flt-1/FLT-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2), are key regulators of tumor angiogenesis and tumor growth. The purpose of this study was to determine the antiangiogenic and antitumor efficacies of a vasculature-targeting fusion toxin (VEGF(121)/rGel) composed of the VEGF-A isoform VEGF(121) linked with a G(4)S tether to recombinant plant toxin gelonin (rGel) in an orthotopic glioblastoma mouse model by use of noninvasive in vivo bioluminescence imaging (BLI), MRI, and PET. METHODS: Tumor-bearing mice were randomized into 2 groups and balanced according to BLI and MRI signals. PET with (64)Cu-1,4,7,10-tetraazacyclododedane-N,N',N'',N'''-tetraacetic acid (DOTA)-VEGF(121)/rGel was performed before VEGF(121)/rGel treatment. (18)F-Fluorothymidine ((18)F-FLT) scans were obtained before and after treatment to evaluate VEGF(121)/rGel therapeutic efficacy. In vivo results were confirmed with ex vivo histologic and immunohistochemical analyses. RESULTS: Logarithmic transformation of peak BLI tumor signal intensity revealed a strong correlation with MRI tumor volume (r = 0.89, n = 14). PET with (64)Cu-DOTA-VEGF(121)/rGel before treatment revealed a tumor accumulation (mean +/- SD) of 11.8 +/- 2.3 percentage injected dose per gram at 18 h after injection, and the receptor specificity of the tumor accumulation was confirmed by successful blocking of the uptake in the presence of an excess amount of VEGF(121). PET with (18)F-FLT revealed significant a decrease in tumor proliferation in VEGF(121)/rGel-treated mice compared with control mice. Histologic analysis revealed specific tumor neovasculature damage after treatment with 4 doses of VEGF(121)/rGel; this damage was accompanied by a significant decrease in peak BLI tumor signal intensity. CONCLUSION: The results of this study suggest that future clinical multimodality imaging and therapy with VEGF(121)/rGel may provide an effective means to prospectively identify patients who will benefit from VEGF(121)/rGel therapy and then stratify, personalize, and monitor treatment to obtain optimal survival outcomes.

Spinal gout in a renal transplant patient: a case report and literature review.

BACKGROUND: Gout in the axial spine is rare. We present a case report on a renal transplant patient who developed fever and acute back pain at the L5 through S1 level secondary to sodium urate deposits. We review the literature on this rare disease and propose a management algorithm based on a resulting analysis. CASE DESCRIPTION: A 37-year-old man with a history of gout and a renal transplant for IgA nephropathy presented with acute back pain and fever without evidence of neurological deficits. Magnetic resonance imaging revealed a uniformly contrast-enhancing infiltrative process involving the right pedicle, lamina, and inferior facet of the L5 vertebra. Computed tomography-guided needle biopsy revealed a friable white tissue consistent with sodium urate crystals. Conservative treatment with steroids and narcotics was used with good symptomatic relief. CONCLUSION: Although few cases of gout involving the spine have been reported, its prevalence is likely grossly underestimated. Most patients have a history of gout and have elevated levels of serum urate level on presentation. The disease most commonly involves the lumbar spine. Patients usually have neurological deficits on presentation, and surgical decompression produces favorable outcomes. However, conservative medical management is appropriate for those with back pain only. Aggressive control of hyperuricemia is essential regardless of the method of treatment.

Glutaric acidemia type I: a neurosurgical perspective. Report of two cases.

Glutaric acidemia type I (GA-I) is a rare, autosomal recessive metabolic disorder that leads to severe dystonia, basal ganglia degeneration, and bilaterally enlarged anterior middle cranial fossae. The current management of this disease includes early diagnosis with newborn screening, prevention of catabolism, carnitine supplementation, and a strict dietary protein restriction. Neurosurgical evaluation and intervention may be necessary in patients with structural lesions associated with this disease. In this report, the authors present two pediatric patients with GA-I and discuss the neurosurgical aspects of this rare medical disorder.

Vascular endothelial growth factor and vascular endothelial growth factor receptor inhibitors as anti-angiogenic agents in cancer therapy.

New blood vessel formation (angiogenesis) is fundamental to the process of tumor growth, invasion, and metastatic dissemination. The vascular endothelial growth factor (VEGF) family of ligands and receptors are well established as key regulators of these processes. VEGF is a glycoprotein with mitogenic activity on vascular endothelial cells. Specifically, VEGF-receptor pathway activation results in signaling cascades that promote endothelial cell growth, migration, differentiation, and survival from pre-existing vasculature. Thus, the role of VEGF has been extensively studied in the pathogenesis and angiogenesis of human cancers. Recent identification of seven VEGF ligand variants (VEGF [A-F], PIGF) and three VEGF tyrosine kinase receptors (VEGFR- [1-3]) has led to the development of several novel inhibitory compounds. Clinical trials have shown inhibitors to this pathway (anti-VEGF therapies) are effective in reducing tumor size, metastasis and blood vessel formation. Clinically, this may result in increased progression free survival, overall patient survival rate and will expand the potential for combinatorial therapies. Having been first described in the 1980s, VEGF patenting activity since then has focused on anti-cancer therapeutics designed to inhibit tumoral vascular formation. This review will focus on patents which target VEGF-[A-F] and/or VEGFR-[1-3] for use in anti-cancer treatment.

Integrin alpha v beta 3 antagonists for anti-angiogenic cancer treatment.

Direct contact between cellular and extracellular matrix (ECM) proteins is necessary for a diverse array of physiologic processes including cellular activation, migration, proliferation, and differentiation. These direct interactions are modulated by cell adhesion molecules (CAMs) such as integrins, selectins, cadherins, and immunoglobulins. Integrin signaling also plays a key role in tumor growth, angiogenesis, and metastasis. Recent advances in the discovery and characterization of CAMs and their receptors, most notably integrin alpha(v)beta(3), and the clarification of their roles in disease states have laid the groundwork for the development and clinical implementation of novel anti-cancer treatments. Integrin alpha (v)beta(3) is a glycoprotein membrane receptor which recognizes ECM proteins expressing an arginine-glycine-aspartic acid (RGD) peptide sequence. The receptor is highly expressed on activated tumor endothelial cells, but not resting endothelial cells and normal organ systems, thus making alpha(v)beta(3) an appropriate target for anti-angiogenic therapeutics. In addition, alpha(v)beta(3) is also expressed on tumor cells, allowing for both tumor cell and tumor vasculature targeting of anti-integrin therapy. Throughout the past decade, numerous patents have been published and issued using alpha(v)beta(3) antagonists for the prevention and/or treatment of cancer, with many antagonists demonstrating positive pre-clinical anti-angiogenic and anti-tumor results. This review will focus on the key points and distinguishing factors for patents which use antibodies, RGD peptides, non-RGD peptides, peptidomimetics, and amine salts as alpha(v)beta(3) antagonists.

In vivo near-infrared fluorescence imaging of integrin alphavbeta3 in an orthotopic glioblastoma model.

PURPOSE: Expression of cell adhesion molecule integrin alpha(v)beta(3) is significantly up-regulated during tumor growth, and sprouting of tumor vessels and correlates well with tumor aggressiveness. The purpose of this study was to visualize tumor integrin alpha(v)beta(3) expression in vivo by using near-infrared fluorescence (NIRF) imaging of Cy5.5-linked cyclic arginine-glycine-aspartic acid (RGD) peptide in an orthotopic brain tumor model. PROCEDURES: U87MG glioma cells transfected with the firefly luciferase gene were stereotactically injected into nude mice in the right frontal lobe. Bioluminescence imaging (BLI) using D: -luciferin substrate and small animal magnetic resonance imaging (MRI) using gadolinium contrast enhancement were conducted weekly after tumor cell inoculation to monitor intracranial tumor growth. Integrin alpha(v)beta(3) expression was assessed by using a three-dimensional optical imaging system (IVIS 200) 0-24 hours after administration of 1.5 nmol monomeric Cy5.5-RGD via the tail vein. Animals were injected intravenously with both Texas Red-tomato lectin and Cy5.5-RGD prior to sacrifice to visualize peptide localization to tumor vasculature using histology. RESULTS: Fluorescence microscopy demonstrated specific Cy5.5-RGD binding to both U87MG tumor vessels and tumor cells with no normal tissue binding. NIRF imaging showed highest tumor uptake and tumor to normal brain tissue ratio two hours postinjection (2.64 +/- 0.20). Tumor uptake of Cy5.5-RGD was effectively blocked by using unlabeled c(RGDyK), and injection of Cy5.5 dye alone showed nonspecific binding. CONCLUSIONS: Optical imaging via BLI and NIRF offer a simple, effective, and rapid technique for noninvasive in vivo monitoring and semiquantitative analysis of intracranial tumor growth and integrin alpha(v)beta(3) expression. This study suggests that NIRF via fluorescently labeled RGD peptides may provide enhanced surveillance of tumor angiogenesis and anti-integrin treatment efficacy in orthotopic brain tumor models.