3D mapping of neuronal migration in the embryonic mouse brain with magnetic resonance microimaging.

A prominent feature of the developing mammalian brain is the widespread migration of neural progenitor (NP) cells during embryogenesis. A striking example is provided by NP cells born in the ventral forebrain of mid-gestation stage mice, which subsequently migrate long distances to their final positions in the cortex and olfactory bulb. Previous studies have used two-dimensional histological methods, making it difficult to analyze three-dimensional (3D) migration patterns. Unlike histology, magnetic resonance microimaging (micro-MRI) is a non-destructive, quantitative and inherently 3D imaging method for analyzing mouse embryos. To allow mapping of migrating NP cells with micro-MRI, cells were labeled in situ in the medial (MGE) and lateral (LGE) ganglionic eminences, using targeted in utero ultrasound-guided injection of micron-sized particles of iron-oxide (MPIO). Ex vivo micro-MRI and histology were then performed 5-6days after injection, demonstrating that the MPIO had magnetically labeled the migrating NP populations, which enabled 3D visualization and automated segmentation of the labeled cells. This approach was used to analyze the distinct patterns of migration from the MGE and LGE, and to construct rostral-caudal migration maps from each progenitor region. Furthermore, abnormal migratory phenotypes were observed in Nkx2.1(-/-) embryos, most notably a significant increase in cortical neurons derived from the Nkx2.1(-/-) LGE. Taken together, these results demonstrate that MPIO labeling and micro-MRI provide an efficient and powerful approach for analyzing 3D cell migration patterns in the normal and mutant mouse embryonic brain.

Transmantle sign in focal cortical dysplasia: a unique radiological entity with excellent prognosis for seizure control.

OBJECT: Focal cortical dysplasia (FCD) represents a spectrum of developmental cortical abnormalities and is one of the most common causes of intractable epilepsy in children and young adults. Outcomes after surgery for FCD are highly variable, and prognosticators of seizure freedom are unclear. In a subset of FCDs, a transmantle sign is observed on imaging that focally spans the entire cerebral mantle from the ventricle to the cortical surface. The aim of this study was to characterize seizure control outcomes and prognostic significance of the transmantle sign in FCD epilepsy. METHODS: Fourteen patients with the transmantle sign underwent epilepsy surgery for medically refractory epilepsy. Thirteen patients underwent resective surgery and 1 underwent multiple subpial transections with vagus nerve stimulator placement. Patient demographics, MRI, electroencephalography, intraoperative electrocorticography (ECoG), and pathology were reviewed. The results of this series were compared with those of 114 previously reported patients with FCD without the transmantle sign. RESULTS: All patients were found to have childhood seizure onset and concordant MRI and ECoG findings. The primary MRI findings associated with transmantle sign included gray-white junction blurring, appearance of cortical thickening, T2 or FLAIR abnormality, and bottom-of-the-sulcus dysplasia. The transmantle sign was usually a focal finding, typically confined to 1 or several gyri with well-circumscribed epileptic tissue. Correlation of the transmantle sign with FCD histopathological subtypes was highly variable. Patients who underwent complete resection of MRI and ECoG abnormalities (12 of 13 patients) became seizure free. When compared with 114 FCD patients without the transmantle sign, patients with the transmantle sign showed significantly improved seizure-free outcomes after complete resections (p = 0.04). CONCLUSIONS: The presence of the transmantle sign in patients with medically refractory partial epilepsy is associated with highly favorable seizure control outcomes after surgical treatment.

Role of fusion of prone FDG-PET and magnetic resonance imaging of the breasts in the evaluation of breast cancer.

The purpose of this study is to report further about the statistically significant results from a prospective study, which suggests that fusion of prone F-18 Fluoro-deoxy-glucose (FDG) positron emission tomography (PET) and magnetic resonance (MR) breast scans increases the positive predictive value (PPV) and specificity for patients in whom the MR outcome alone would be nonspecific. Thirty-six women (mean age, 43 years; range, 24-65 years) with 90 lesions detected on MR consented to undergo a FDG-PET scan. Two blinded readers evaluated the MR and the computer tomography (CT) attenuation-corrected prone FDG-PET scans side-by-side, then after the volumes were superimposed (fused). A semiautomatic, landmark-based program was used to perform nonrigid fusion. Pathology and radiologic follow-up were used as the reference standard. The sensitivity, specificity, PPV, negative predictive value (NPV), and accuracy (with 95% confidence intervals) for MR alone, FDG-PET alone, and fused MR and FDG-PET were calculated. The median lesion size measured from the MR was 2.5 cm (range, 0.5-10 cm). Histologically, 56 lesions were malignant, and 15 were benign. Nineteen lesions were benign after 20-47 months of clinical and radiologic surveillance. The sensitivity of MR alone was 95%, FDG-PET alone was 57%, and fusion was 83%. The increase in PPV from 77% in MR alone to 98% when fused and the increase in specificity from 53% to 97% were statistically significant (p < 0.05). The false-negative rate on FDG-PET alone was 26.7%, and after fusion this number was reduced to 9%. FDG-PET and MR fusions were helpful in selecting which lesion to biopsy, especially in women with multiple suspicious MR breast lesions.

Mn enhancement and respiratory gating for in utero MRI of the embryonic mouse central nervous system.

The mouse is the preferred model organism for genetic studies of mammalian brain development. MRI has potential for in utero studies of mouse brain development, but has been limited previously by challenges of maximizing image resolution and contrast while minimizing artifacts due to physiological motion. Manganese (Mn)-enhanced MRI (MEMRI) studies have demonstrated central nervous system (CNS) contrast enhancement in mice from the earliest postnatal stages. The purpose of this study was to expand MEMRI to in utero studies of the embryonic CNS in combination with respiratory gating to decrease motion artifacts. We investigated MEMRI-facilitated CNS segmentation and three-dimensional (3D) analysis in wild-type mouse embryos from midgestation, and explored effects of Mn on embryonic survival and image contrast. Motivated by observations that MEMRI provided an effective method for visualization and volumetric analysis of embryonic CNS structures, especially in ventral regions, we used MEMRI to examine Nkx2.1 mutant mice that were previously reported to have ventral forebrain defects. Quantitative MEMRI analysis of Nkx2.1 knockout mice demonstrated volumetric changes in septum (SE) and basal ganglia (BG), as well as alterations in hypothalamic structures. This method may provide an effective means for in utero analysis of CNS phenotypes in a variety of mouse mutants.

Improving specificity of breast MRI using prone PET and fused MRI and PET 3D volume datasets.

UNLABELLED: MRI is a sensitive method for detecting invasive breast cancer, but it lacks specificity. To examine the effect of combining PET with MRI on breast lesion characterization, a prototype positioning device was fabricated to allow PET scans to be acquired in the same position as MRI scans--that is, prone. METHODS: To test the hypothesis that fusion of (18)F-FDG PET and MRI scans improves detection of breast cancer, 23 patients with suspected recurrent or new breast cancer underwent a routine whole-body PET scan, a prone PET scan of the chest, and a routine breast MRI scan. The attenuation-corrected prone PET and MRI datasets were registered twice by different operators. The fusion results were judged for quality by visual inspection and statistical analysis. A joint reading of the MRI and PET scans side by side and integrated images was performed by a nuclear medicine physician and a radiologist. Sensitivity and specificity of MRI and combined MRI and PET scans were calculated on the basis of pathology reports or at least 1 y of clinical and radiologic follow-up. RESULTS: All fusions were verified to be well matched using specific anatomic criteria. A total of 45 lesions was assessed. Lesion size range was 0.6 to 10.0 cm. Of the 44 breasts examined, 29 were suspicious for cancer, of which 15 were found to be positive on surgical excision. In lesion-by-lesion analysis, sensitivity and specificity of MRI alone were 92% and 52%, respectively; after MRI and PET fusion, they were 63% and 95%, respectively. The positive predictive value and the negative predictive value for MRI alone were 69% and 85%, respectively; after MRI and PET fusion, they were 94% and 69%, respectively. CONCLUSION: Acquisition of prone PET scans using the new positioning device permitted acquisition of prone scans suitable for fusion with breast MRI scans. Fused PET and MRI scans increased the specificity of MRI but decreased the sensitivity in this small group of patients. Additional data are needed to confirm the statistical significance of these preliminary findings.

Prone mammoPET acquisition improves the ability to fuse MRI and PET breast scans.

PURPOSE: This study compared prone acquisition of PET scans with traditional supine acquisition to improve fusion of PET scans with MRI scans and improve evaluation of enhancing breast lesions detected on MRI. MATERIALS AND METHODS: MRI breast scans are acquired in the prone position using a breast coil to allow the breasts to hang pendant. An apparatus was fabricated to allow prone acquisition of PET scans. Fused scans from 2 patients acquired both prone and supine were contrasted with those from 3 patients acquired supine only. All 5 MRI scans were acquired on standard scanners. The PET scans were acquired with a PET/CT unit using a low-dose CT scan for attenuation correction. The PET and MRI volumes were matched twice (using a semiautomated registration method) by different operators. The additional value of fusion was judged using reports from the original (nonfused) MRI and PET, joint rereading of the volumes side by side, and examination of fused images. RESULTS: Of 12 enhancing lesions on breast MRI, 7 demonstrated uptake on PET/CT. In the 3 supine-only cases, the fused images were not interpretable because of the marked distortion of the breasts. In the 2 prone cases, the fused images increased our confidence in characterizing a lesion as benign or malignant. Interpretations were confirmed by clinical follow up in 2 or histologic results in 3 patients. CONCLUSIONS: PET MRI fusion is feasible and may assist in localizing lesions detected on either study. A more extensive study is underway to confirm the value of this fusion technique.

Cellular MRI contrast via coexpression of transferrin receptor and ferritin.

Recently there has been growing interest in the development and use of iron-based contrast agents for cellular imaging with MRI. In this study we investigated coexpression of the transferrin receptor and ferritin genes to induce cellular contrast in a biological system. Expression of transgenic human transferrin receptor and human ferritin H-subunit was induced in a stably transfected mouse neural stem cell line. When grown in iron-rich medium, the transgenic cells accumulated significantly more iron than control cells, with a trend toward an increase in reactive oxygen species, but no detrimental effects on cell viability. This cellular iron significantly increased the transverse relaxivities, R2 and R2*, at 1.5 T and 7 T. By comparing measurements in the same cell samples at 1.5 T and 7 T, we confirmed the expected increase in relaxivity with increasing field strength. Finally, supplemented transgenic cells transplanted into mouse brain demonstrated increased contrast with surrounding neural tissue on T2*-weighted MR brain images compared to controls. These results indicate that dual expression of proteins at different critical points in the iron metabolism pathway may improve cellular contrast without compromising cell viability.