cGMP compliant one-step, one-pot automated [18F]FBnTP production for clinical imaging of mitochondrial activity.

BACKGROUND: 4-[18F]fluorobenzyl-triphenylphosphonium ([18F]FBnTP) is a lipophilic cation PET tracer. The cellular uptake of [18F]FBnTP is correlated with oxidative phosphorylation by mitochondria, which has been associated with multiple critical diseases. To date, [18F]FBnTP has been successfully applied for imaging myocardial perfusion, assessment of severity of coronary artery stenosis, delineation of the ischemic area after transient coronary occlusion, and detection/quantification of apoptosis in various animal models. Recent preclinical and clinical studies have also expanded the possibilities of using [18F]FBnTP in oncological diagnosis and therapeutic monitoring. However, [18F]FBnTP is typically prepared through a tediously lengthy four-step, three-pot reaction and required multiple synthesizer modules; Thus, such an approach remains a challenge for this promising radiopharmaceutical to be implemented for routine clinical studies. Herein, we report an optimized one-step, one-pot automated approach to produce [18F]FBnTP through a single standard commercially-available radiosynthesizer that enables centralized production for clinical use. RESULTS: The fully automated production of [18F]FBnTP took less than 55 min with radiochemical yields ranging from 28.33 ± 13.92% (non-decay corrected), apparent molar activity of 69.23 ± 45.62 GBq/µmol, and radiochemical purities of 99.79 ± 0.41%. The formulated [18F]FBnTP solution was determined to be sterile and colorless with a pH of 4.0-6.0. Our data has indicated no observable radiolysis after 8 h from the time of final product formulation and maximum assay of 7.88 GBq. CONCLUSIONS: A simplified and cGMP-compliant radiosynthesis of [18F]FBnTP has been established on the commercially available synthesizer in high activity concentration and radiochemical purity. While the preclinical and clinical studies using [18F]FBnTP PET are currently underway, the automated approaches reported herein facilitate clinical adoption of this radiotracer and warrant centralized production of [18F]FBnTP for imaging multiple patients.

Simplified and highly-reliable automated production of [18F]FSPG for clinical studies.

BACKGROUND: (S)-4-(3-18F-Fluoropropyl)-L-Glutamic Acid ([18F]FSPG) is a positron emission tomography (PET) tracer that specifically targets the cystine/glutamate antiporter (xc-), which is frequently overexpressed in cancer and several neurological disorders. Pilot studies examining the dosimetry and biodistribution of [18F]FSPG in healthy volunteers and tumor detection in patients with non-small cell lung cancer, hepatocellular carcinoma, and brain tumors showed promising results. In particular, low background uptake in the brain, lung, liver, and bowel was observed that further leads to excellent imaging contrasts of [18F]FSPG PET. However, reliable production-scale cGMP-compliant automated procedures for [18F]FSPG production are still lacking to further increase the utility and clinical adoption of this radiotracer. Herein, we report the optimized automated approaches to produce [18F]FSPG through two commercially available radiosynthesizers capable of supporting centralized and large-scale production for clinical use. RESULTS: Starting with activity levels of 60-85 GBq, the fully-automated process to produce [18F]FSPG took less than 45 min with average radiochemical yields of 22.56 ± 0.97% and 30.82 ± 1.60% (non-decay corrected) using TRACERlab™ FXFN and FASTlab™, respectively. The radiochemical purities were > 95% and the formulated [18F]FSPG solution was determined to be sterile and colorless with the pH of 6.5-7.5. No radiolysis of the product was observed up to 8 h after final batch formulation. CONCLUSIONS: In summary, cGMP-compliant radiosyntheses and quality control of [18F]FSPG have been established on two commercially available synthesizers leveraging high activity concentration and radiochemical purity. While the clinical trials using [18F]FSPG PET are currently underway, the automated approaches reported herein will accelerate the clinical adoption of this radiotracer and warrant centralized and large-scale production of [18F]FSPG.

Simplified and Highly-reliable automated production of [18F]FSPG for clinical studies.

Background (S)-4-(3- 18 F-Fluoropropyl)-L-Glutamic Acid ([ 18 F]FSPG) is a positron emission tomography (PET) tracer that specifically targets the cystine/glutamate antiporter (xc-), which is frequently overexpressed in cancer and several neurological disorders. Pilot studies examining the dosimetry and biodistribution of ([ 18 F]FSPG in healthy volunteers and tumor detection in patients with non-small cell lung cancer, hepatocellular carcinoma, and brain tumors showed promising results. In particular, low background uptake in the brain, lung, liver, and bowel was observed that further leads to excellent imaging contrasts of [ 18 F]FSPG PET. However, reliable production-scale cGMP-compliant automated procedures for [ 18 F]FSPG production are still lacking to further increase the utility and clinical adoption of this radiotracer. Herein, we report the optimized automated approaches to produce [ 18 F]FSPG through two commercially available radiosynthesizers capable of supporting centralized and large-scale production for clinical use. Results Starting with activity levels of 60-85 GBq, the fully-automated process to produce [ 18 F]FSPG took less than 45 minutes with average radiochemical yields of 22.56 ± 0.97% and 30.82 ± 1.60% (non-decay corrected) using TRACERlab™ FXFN and FASTlab™, respectively. The radiochemical purities were > 95% and the formulated [ 18 F]FSPG solution was determined to be sterile and colorless with the pH of 6.5-7.5. No radiolysis of the product was observed up to 8 hours after final batch formulation. Conclusions In summary, cGMP-compliant radiosyntheses and quality control of [ 18 F]FSPG have been established on two commercially available synthesizers leveraging high activity concentration and radiochemical purity. While the clinical trials using [ 18 F]FSPG PET are currently underway, the automated approaches reported herein will accelerate the clinical adoption of this radiotracer and warrant centralized and large-scale production of [ 18 F]FSPG.

Molecular Diagnostic Review of Diffuse Large B-Cell Lymphoma and Its Tumor Microenvironment.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. It is a clinically and morphologically heterogeneous entity that has continued to resist complete subtyping. Molecular subtyping efforts emerged in earnest with the advent of gene expression profiling (GEP). This molecular subtyping approach has continued to evolve simultaneously with others including immunohistochemistry and more modern genomic approaches. Recently, the veritable explosion of genomic data availability and evolving computational methodologies have provided additional avenues, by which further understanding and subclassification of DBLCLs is possible. The goal of this review is to provide a historical overview of the major classification timepoints in the molecular subtyping of DLBCL, from gene expression profiling to present day understanding.

Primary Central Nervous System Anaplastic Large Cell Lymphoma, ALK Positive.

OBJECTIVES: Primary central nervous system anaplastic large cell lymphoma, anaplastic lymphoma kinase positive (primary CNS ALCL, ALK+) is a rare CNS lymphoma whose description is limited to case reports. These tumors have a variable clinical course, and prognosis is primarily determined by age. We present the largest case series to date of primary CNS ALCL, ALK+, with observational data. METHODS: A retrospective search of multiple academic centers was performed to identify cases of primary CNS ALCL, ALK+. We also performed a review of published cases of primary CNS ALCL, ALK+. Clinical history, radiography, pathology, and genetic testing data were obtained to determine the prognostic implications in the context of clinical course. RESULTS: We identified three cases of primary CNS ALCL, ALK+ from our databases. A literature review identified 30 published reports of 31 individual cases. Clinical features for the combined 34 cases included a median age of 18.5 years, with a male to female ratio of 4.7:1, and the most common symptom was headache. Genetic studies demonstrated an ALK rearrangement by fluorescence in situ hybridization, and a gene fusion assay confirmed an NPM1-ALK gene fusion in one case. CONCLUSIONS: We present the largest case series to date of a rare primary CNS lymphoma with additional diagnostic and clinical information.

The impact of pathology grossing protocol measures to improve pathologic nodal staging in lung cancer.

OBJECTIVE: Accurate assessment of lymph node (LN) status is essential for proper staging of resected lung cancer specimens. Here, we assessed pathology-centric interventions to increase the number of peribronchial LNs identified and evaluated in anatomic lung cancer resection specimens as part of a quality improvement initiative. MATERIALS AND METHODS: All non-small cell lung cancer (NSCLC) anatomic resection specimens from 2017 to 2020 were evaluated, comprising two years pre-intervention and one year post-intervention. We instituted 3 measures to increase peribronchial LN yield: 1) educational grossing sessions for pathology assistants and residents, 2) directions to submit additional peribronchial tissue if no LNs were identified grossly, and 3) a hard-stop prior to sign-out by the attending pathologist if no peribronchial LNs were identified. RESULTS: Of the total 227 resection specimens for NSCLC, 107/151 (70.9%) of specimens prior to the intervention had peribronchial LNs identified, whereas after the intervention significantly more (66/76, 86.8%, p < 0.01) specimens had peribronchial LNs identified. In addition, the mean number of peribronchial LNs identified significantly increased from 2.7 ± 3.3 pre-intervention to 4.3 ± 4.0 post-intervention (p < 0.001). Further analysis revealed a strong correlation between peribronchial LN metastases with both overall tumor size and invasive component size (for adenocarcinomas), correlation coefficient 0.974, p < 0.0001. CONCLUSION: Establishing focused grossing measures by pathology led to a significant increase in the number of peribronchial LNs identified and assessed during histopathologic evaluation of anatomic lung cancer resection specimens. Larger tumors are more likely to have occult peribronchial LN metastases, which may warrant more aggressive peribronchial LN assessment for larger tumors.

Molecular Subtyping of Diffuse Large B-Cell Lymphoma Using a Novel Quantitative RT-PCR Assay.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. Cell-of-origin classification in DLBCL has identified activated B cell (ABC) and germinal center B cell (GCB) as two major subtypes. Patients with the ABC subtype show reduced overall survival with standard therapies. Development of a quantitative RT-PCR-based lymphoma cell-of-origin (LCOO) assay to determine ABC, GCB, and unclassifiable subtypes in formalin-fixed, paraffin-embedded tissue (FFPET) DLBCL samples is reported. The LCOO classifier was trained on two DLBCL cohorts with validation performed by using an analytical grade assay in an independent cohort of 60 FFPET DLBCL samples. In the validation cohort, LCOO classification was 88.1%, 84.7%, and 84.7% concordant with microarray, immunohistochemistry (Hans classification), and Lymphoma Subtyping Test, respectively. Importantly, LCOO and Lymphoma Subtyping Test assays commonly assigned subtypes in 17 (94.4%) of 18 ABC samples and 34 (89.5%) of 38 GCB DLBCL samples from this cohort. Progression-free survival and overall survival of ABC and GCB subtypes, as classified by all platforms, were not significantly different in the validation cohort. LCOO classification using publicly available microarray gene expression from two independent data sets (414 fresh frozen and 474 FFPET DLBCL biopsies) revealed a significantly worse outcome for the ABC subtype compared with that of the GCB subtype. Thus, a sensitive, reproducible, LCOO assay developed on an easy to standardize quantitative RT-PCR platform may be an important clinical tool for DLBCL cell-of-origin classification.

Prostate-Specific Membrane Antigen-Targeted Radiopharmaceuticals in Diagnosis and Therapy of Prostate Cancer: Current Status and Future Perspectives.

Prostate cancer is the most common cancer to affect men in the United States and the second most common cancer in men worldwide. Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET) imaging has become increasingly popular as a novel molecular imaging technique capable of improving the clinical management of patients with prostate cancer. To date, several 68Ga and 18F-labeled PSMA-targeted molecules have shown promising results in imaging patients with recurrent prostate cancer using PET/computed tomography (PET/CT). Studies of involving PSMA-targeted radiopharmaceuticals also suggest a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and methylene diphosphonate bone scintigraphy) and 11C/18F-choline PET/CT. In addition, PSMA-617 and PSMA I&T ligands can be labeled with α- and ß-emitters (e.g., 225Ac, 90Y, and 177Lu) and serve as a theranostic tool for patients with metastatic prostate cancer. While the clinical impact of such concept remains to be verified, the preliminary results of PSMA molecular radiotherapy are very encouraging. Herein, we highlighted the current status of development and future perspectives of PSMA-targeted radiopharmaceuticals and their clinical applications.

False-Negative Urine Human Chorionic Gonadotropin Testing in the Clinical Laboratory.

BACKGROUND: Human chorionic gonadotropin (hCG) assays are used to detect pregnancy, and urine point-of-care tests are frequently used to triage patients. Under certain conditions, urine tests can fail to detect pregnancy, which can have serious consequences for patient management. OBJECTIVES: To understand the prevalence of different factors contributing to false-negative urinary hCG testing results at our institution. METHODS: Clinical data for patients with negative urine hCG results and subsequent positive or equivocal serum hCG results within a 1-year period were reviewed. RESULTS: Out of 9447 negative urine hCG results, 11 potential missed diagnoses were identified, with early gestational age as the most common factor, followed by ß-core hook effects. CONCLUSIONS: Although false-negative urine hCG test results are rare, understanding the commonly encountered reasons for inaccurate testing results can help clinical centers develop strategies to minimize risk for patients.

Fully automated preparation of 68Ga-PSMA-11 at curie level quantity using cyclotron-produced 68Ga for clinical applications.

68Ga-PSMA-11 is currently one of the most investigated PET agents for imaging both recurrent prostate cancer and relevant metastases; however, the production and distribution of 68Ga-PSMA-11 is limited to a supply of only a few daily doses when using a commercially available 68Ge/68Ga generator. 68Ge/68Ga generators deliver only a modest amount of activity, up to 1850 MBq (50 mCi), when new, but it decreases with time. Additionally, the production of 68Ga/68Ge generators has not been able to meet the increasing demand of 68Ga radiotracers. In response to the need for a more economically viable alternative, the focus of this study was to provide a simple and efficient method for producing 68Ga-PSMA-11, using cyclotron-produced 68Ga that is ready for routine clinical practice.

The Role of Staging Laparoscopy in Resectable and Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis.

AIM: The study aimed to determine the additional value of staging laparoscopy in patients with pancreatic cancer deemed potentially resectable based on computed tomography imaging. METHODS: A systematic literature search was performed using MEDLINE and the Cochrane Register of Controlled Trials (January 1995 to June 2017). Primary outcome measures were the overall yield and sensitivity to detect non-resectable disease. Quality of studies was assessed with the Newcastle-Ottawa Scale. RESULTS: From 156 records, 15 studies including 2,776 patients met the inclusion criteria. In 12 studies, reporting outcomes on 1,756 patients with resectable disease after standard imaging, 350 (20%, range 14-38%) cases of non-resectable cancer were detected with staging laparoscopy. In 3 studies on 242 patients with locally advanced disease after standard imaging, staging laparoscopy detected metastases in 86 patients (36%). The failure rate of staging laparoscopy to detect non-resectable disease was 5% (64 of 1,406). CONCLUSION: Staging laparoscopy reduces the non-therapeutic laparotomy rate, and in locally advanced or borderline resectable disease, staging laparoscopy could more accurately select patients for neoadjuvant protocols.

Discordant loss of mismatch repair proteins in advanced endometrial endometrioid carcinoma compared to paired primary uterine tumors.

OBJECTIVE: A subset of endometrial cancer is characterized by deficiencies in the mismatch repair (MMR) pathway. MMR testing is a well-established tool to screen for Lynch syndrome, but has also become a companion diagnostic test for immunotherapy. We compared the MMR status of primary and paired metastatic endometrial cancer to determine whether MMR deficiency can occur specifically in advanced endometrial cancer compared to primary tumor. METHODS: Matched primary uterine and metastatic endometrioid adenocarcinoma from 2009 to 2018 at our institution were identified. PMS2 and MSH6 protein expression in metastatic and matched primary tumor was assessed using clinically validated immunohistochemistry methods for Lynch syndrome screening. MLH1 promoter hypermethylation and microsatellite instability (MSI) were performed in discordant cases. RESULTS: 29 patients were identified with paired primary endometrial endometrioid adenocarcinoma and metastasis or recurrence after the original hysterectomy. Fourteen of 29 cases (48.2%, 14/29) were found to be MMR deficient at the metastatic or recurrent site. Two patients (6.9%, 2/29) showed discordant MMR status with PMS2 protein loss at the metastatic sites and intact expression in the primary uterine tumors. Both discordant cases exhibited abnormal subclonal loss at primary site and MLH1 promoter hypermethylation. High levels of microsatellite instability (MSI-H) was confirmed in one discordant metastatic site. CONCLUSION: Advanced endometrial cancer can rarely (~7%) show somatic loss of MMR protein expression in recurrent or metastatic sites compared to matched paired primary tumor. MMR testing of recurrent or metastasis should be considered for guiding immunotherapy if primary uterine tumor exhibits abnormal subclonal MMR loss.

miR-223 potentially targets SWI/SNF complex protein SMARCD1 in atypical proliferative serous tumor and high-grade ovarian serous carcinoma.

Ovarian cancer is the fifth most common cancer in women worldwide and has the highest mortality amongst gynecological cancers. miRNAs are a class of non-coding RNAs, approximately 22 nt long, that negatively regulate gene expression and have roles in cell growth, differentiation, metabolism, apoptosis and tumorigenesis. Dysregulated miRNA-223 expression has been implicated in a wide range of cancer subtypes. SMARCD1 is an integral protein component of the SWI/SNF complex, which remodels chromatin, and which has important roles in transcriptional control, DNA replication, recombination and repair. In this study, we examined whether the expression levels of miR-223 and SMARCD1 are altered in ovarian serous neoplasia and whether miR-223 functionally regulates the gene and protein expression of SMARCD1 in vivo, as has been predicted by in silico methods. Benign, atypical proliferative serous tumors (borderline) and malignant serous tumors (n = 144) were laser-capture microdissected, and relative expression levels of miR-223 and SMARCD1 were quantified by RT-PCR. Ovarian cancer cell line OC316 was reverse transfected with a miR-223 mimic, and relative expression levels of miR-223 and SMARCD1 were quantified by reverse-transcription polymerase chain reaction; protein expression of SMARCD1 was evaluated by Western blot. miR-223 expression was up-regulated in high-grade ovarian serous carcinoma samples (median RQ = 4.8881, P = .0045), whilst SMARCD1 was down-regulated (median RQ = 0.5107, P = .0492). In OC316 cells transfected with a miR-223 mimic, SMARCD1 gene expression was down-regulated 3-fold (P = .001), and SMARCD1 protein expression was down-regulated 2-fold (P = .002). These results suggest a regulatory role for miR-223 in ovarian serous neoplasia, linking it with SMARCD1.

Diffuse Alveolar Hemorrhage in Systemic Lupus Erythematosus: Histopathologic Features and Clinical Correlations.

The case of a 16-year-old African-American girl with systemic lupus erythematosus, who developed diffuse alveolar hemorrhage with fatal consequences, is described. Diffuse alveolar hemorrhage is a rare but serious complication of systemic lupus. It occurs in three distinct but overlapping phenotypes, acute capillaritis, bland pulmonary hemorrhage, and diffuse alveolar damage, each of which is associated with a different group of underlying conditions. Diffuse alveolar hemorrhage is a medical emergency: choice of treatment depends on early diagnosis and determination of the underlying etiology. Acute infection, superimposed on diffuse alveolar hemorrhage in the setting of immune compromise, is often a terminal event, as in this case.

Helmet-Wearing Practices and Barriers in Toronto Bike-Share Users: a Case-Control Study.

BACKGROUND: Helmet use among bike-share users is low. We sought to characterize helmet-use patterns, barriers to helmet use, and cycling safety practices among bike-share users in Toronto. METHODS: A standardized survey of public bike-share program (PBSP) users at semi-random distribution of PBSP stations was undertaken. By maintaining a ratio of one helmet-wearer (HW): two non-helmet-wearers (NHW) per survey period, we controlled for location, day, time, and weather. RESULTS: Surveys were completed on 545 (180 HW, 365 NHW) unique users at 48/80 PBSP locations, from November 2012 to August 2013. More females wore helmets (F: 41.1%, M: 30.9%, p=0.0423). NHWs were slightly younger than HWs (NHW mean age 34.4 years vs HW 37.3, p=0.0018). The groups did not differ by employment status, education, or income. Helmet ownership was lower among NHWs (NHW: 62.4% vs HW: 99.4%, p<0.0001), as was personal bike ownership (NHW: 65.8%, vs HW: 78.3%, p=0.0026). NHWs were less likely to always wear a helmet on personal bikes (NHW: 22.2% vs HW: 66.7%, p<0.0001), and less likely to wear a helmet always or most of the time on PBSP (NHW: 5.8% vs HW: 92.3%, p<0.0001). Both groups, but more HWs, had planned to use PBSP when leaving their houses (HW: 97.2% vs NHW: 85.2%, p<0.0001), primarily to get to work (HW: 88.3% vs NHW: 84.1%, p=0.19). NHWs were more likely to report that they would wear a helmet more (NHW: 61.4% vs HW: 13.9%, p<0.0001), and/or cycle less (NHW: 22.5% vs HW: 4.4%) if helmet use was mandatory. CONCLUSIONS: PBSP users surveyed appear to make deliberate decisions regarding helmet use. NHWs tended to be male, slightly younger, and less likely to use helmets on their personal bikes. As Toronto cyclists who do not wear helmets on PBSP generally do not wear helmets on their personal bikes, interventions to increase helmet use should target both personal and bike-share users. Legislating helmet use and provision of rental helmets could improve helmet use among bike-share users, but our results suggest some risk of reduced cycling with legislation.

A dual magnetic resonance imaging/fluorescent contrast agent for Cathepsin-D detection.

Currently there are no approved biomarkers for the pre-symptomatic diagnosis of Alzheimer's disease (AD). Cathepsin-D (Cat-D) is a lysosomal protease that is present at elevated levels in amyloid plaques and neurons in patients with AD and is also elevated in some cancers. We have developed a magnetic resonance imaging (MRI)/fluorescent contrast agent to detect Cat-D enzymatic activity. The purpose of this study was to investigate the cellular and tissue uptake of this MRI/fluorescent contrast agent. The agent consists of an MRI probe [DOTA-caged metal ion (Gd³âº or Tm³âº)] and a fluorescent probe coupled to a cell-penetrating-peptide sequence by a Cat-D recognition site. The relaxivity of Gd³âº-DOTA-CAT(cleaved) was measured in 10% heat-treated bovine serum albumin (BSA) phantoms to assess contrast efficacy at magnetic fields ranging from 0.24 mT to 9.4 T. In vitro, Tm³âº-DOTA-CAT was added to neuronal SN56 cells over-expressing Cat-D and live-cell confocal microscropy was performed at 30 min. Tm³âº-DOTA-CAT was also intravenously injected into APP/PS1-dE9 Alzheimer's disease mice (n = 9) and controls (n = 8). Cortical and hippocampal uptake was quantified at 30, 60 and 120 min post-injection using confocal microscopy. The liver and kidneys were also evaluated for contrast agent uptake. The relaxivity of Gd³âº-DOTA-CAT(cleaved) was 3.3 (mM s)⁻¹ in 10% BSA at 9.4 T. In vitro, cells over-expressing Cat-D preferentially took up the contrast agent in a concentration-dependent manner. In vivo, the contrast agent effectively crossed the blood-brain barrier and exhibited a distinct time course of uptake and retention in APP/PS1-dE9 transgenic mice compared with age-matched controls. At clinical and high magnetic field strengths, Gd³âº-DOTA-CAT produced greater T1 relaxivity than Gd³âº-DTPA. Tm³âº-DOTA-CAT was taken up in a dose-dependent manner in cells over-expressing Cathepsin-D and was shown to transit the blood-brain barrier in vivo. This strategy may be useful for the in vivo detection of enzyme activity and for the diagnosis of Alzheimer's disease.

A novel MRI-compatible brain ventricle phantom for validation of segmentation and volumetry methods.

PURPOSE: To create a standardized, MRI-compatible, life-sized phantom of the brain ventricles to evaluate ventricle segmentation methods using T(1) -weighted MRI. An objective phantom is needed to test the many different segmentation programs currently used to measure ventricle volumes in patients with Alzheimer's disease. MATERIALS AND METHODS: A ventricle model was constructed from polycarbonate using a digital mesh of the ventricles created from the 3 Tesla (T) MRI of a subject with Alzheimer's disease. The ventricle was placed in a brain mold and surrounded with material composed of 2% agar in water, 0.01% NaCl and 0.0375 mM gadopentetate dimeglumine to match the signal intensity properties of brain tissue in 3T T(1) -weighted MRI. The 3T T(1) -weighted images of the phantom were acquired and ventricle segmentation software was used to measure ventricle volume. RESULTS: The images acquired of the phantom successfully replicated in vivo signal intensity differences between the ventricle and surrounding tissue in T(1) -weighted images and were robust to segmentation. The ventricle volume was quantified to 99% accuracy at 1-mm voxel size. CONCLUSION: The phantom represents a simple, realistic and objective method to test the accuracy of lateral ventricle segmentation methods and we project it can be extended to other anatomical structures.