Oculodentodigital Dysplasia: A Hypomyelinating Leukodystrophy with a Characteristic MRI Pattern of Brain Stem Involvement.

Oculodentodigital dysplasia, a rare genetic disorder caused by mutations in the gene encoding gap junction protein 1, classically presents with typical facial features, dental and ocular anomalies, and syndactyly. Oligosymptomatic patients are common and difficult to recognize, in particular if syndactyly is absent. Neurologic manifestation occurs in approximately 30% of patients, and leukodystrophy or T2 hypointensity of gray matter structures or both have been noted in individual patients. To investigate MR imaging changes in oculodentodigital dysplasia, we retrospectively and systematically reviewed 12 MRIs from 6 genetically confirmed patients. Diffuse supratentorial hypomyelination, T2-hypointense Rolandic and primary visual cortex, and symmetric involvement of middle cerebellar peduncle, pyramidal tract, and medial lemniscus was present in all, T2-hypointense pallidum and dentate nucleus in 2 patients each. This consistent, characteristic pattern of diffuse supratentorial hypomyelination and brain stem involvement differs from other hypomyelinating and nonhypomyelinating leukodystrophies with brain stem involvement, and its recognition should trigger genetic testing for oculodentodigital dysplasia.

Diagnostic Accuracy of Neuroimaging to Delineate Diffuse Gliomas within the Brain: A Meta-Analysis.

BACKGROUND: Brain imaging in diffuse glioma is used for diagnosis, treatment planning, and follow-up. PURPOSE: In this meta-analysis, we address the diagnostic accuracy of imaging to delineate diffuse glioma. DATA SOURCES: We systematically searched studies of adults with diffuse gliomas and correlation of imaging with histopathology. STUDY SELECTION: Study inclusion was based on quality criteria. Individual patient data were used, if available. DATA ANALYSIS: A hierarchic summary receiver operating characteristic method was applied. Low- and high-grade gliomas were analyzed in subgroups. DATA SYNTHESIS: Sixty-one studies described 3532 samples in 1309 patients. The mean Standard for Reporting of Diagnostic Accuracy score (13/25) indicated suboptimal reporting quality. For diffuse gliomas as a whole, the diagnostic accuracy was best with T2-weighted imaging, measured as area under the curve, false-positive rate, true-positive rate, and diagnostic odds ratio of 95.6%, 3.3%, 82%, and 152. For low-grade gliomas, the diagnostic accuracy of T2-weighted imaging as a reference was 89.0%, 0.4%, 44.7%, and 205; and for high-grade gliomas, with T1-weighted gadolinium-enhanced MR imaging as a reference, it was 80.7%, 16.8%, 73.3%, and 14.8. In high-grade gliomas, MR spectroscopy (85.7%, 35.0%, 85.7%, and 12.4) and 11C methionine-PET (85.1%, 38.7%, 93.7%, and 26.6) performed better than the reference imaging. LIMITATIONS: True-negative samples were underrepresented in these data, so false-positive rates are probably less reliable than true-positive rates. Multimodality imaging data were unavailable. CONCLUSIONS: The diagnostic accuracy of commonly used imaging is better for delineation of low-grade gliomas than high-grade gliomas on the basis of limited evidence. Improvement is indicated from advanced techniques, such as MR spectroscopy and PET.

Retinoblastoma: value of dynamic contrast-enhanced MR imaging and correlation with tumor angiogenesis.

BACKGROUND AND PURPOSE: Noninvasive evaluation of retinoblastoma treatment response has become more important due to increased use of eye-sparing treatments. We evaluated the relation between DCE-MR imaging and histopathologic parameters to determine the value of DCE-MR imaging in assessing tumor angiogenesis and prognostic features. MATERIALS AND METHODS: Fifteen consecutive patients with retinoblastoma (mean age, 24 months; range, 2-70 months) undergoing enucleation as the primary treatment (15 eyes) were scanned at 1.5T by using dedicated surface coils. Pretreatment DCE-MR imaging of the most affected eye was evaluated by 2 observers by using curve-pattern analysis, with the first 5 minutes of each curve and the full time-series described as κ(5min) and κ(17min), respectively. Assessed histopathologic and immunologic parameters included optic nerve invasion, choroid invasion, MVD, tumor necrosis, and expression of VEGF and Flt-1. RESULTS: The median value of κ(5min) was 1.28 (range, 0.87-2.07) and correlated positively with MVD (P = .008). The median value of κ(17min) was 1.33 (range, 0.35-3.08) and correlated negatively with tumor necrosis (P = .002). Other histopathologic and immunohistopathologic parameters did not correlate with DCE-MR imaging parameters. Interobserver agreement was 0.53 for κ(5min) and 0.91 for κ(17min). CONCLUSIONS: In retinoblastoma, the early phase of the DCE time curve positively correlates with MVD, while the presence of late enhancement is correlated with necrosis. Thus, the potential for DCE-MR imaging to noninvasively assess tumor angiogenesis and necrosis in retinoblastoma is promising and warrants further investigation.

Diffusion-weighted MR imaging in head and neck cancer: comparison between half-fourier acquired single-shot turbo spin-echo and EPI techniques.

BACKGROUND AND PURPOSE: Several studies have reported on the clinical utility of DWI in head and neck cancer, but none of these studies compared HASTE with EPI-DWI in patients with head and neck cancer. The aim of our study was to compare detection and delineation of primary tumors and lymph nodes by using HASTE and EPI-DWI techniques in patients with HNSCC. MATERIALS AND METHODS: Twelve patients with HNSCC and a total of 12 primary tumors and 77 visualized lymph nodes on MR imaging underwent DWI by using both EPI-based and HASTE techniques. Interobserver agreement for detection, delineation, and ADC values of primary tumors and lymph nodes was assessed by 2 radiologists, and artifacts for both DWI techniques were described. RESULTS: The number of lesions (primary tumors and lymph nodes) identified on pretreatment EPI-DWI was higher compared with pretreatment HASTE-DWI, with means of total lesions of 88.5 and 69.0, respectively. Delineation of lesions was also better on pretreatment EPI-DWI compared with pretreatment HASTE-DWI, with means of well-delineated lesions of 80.5 and 27.5, respectively. Both EPI- and HASTE-DWI showed good interobserver agreement between radiologists of ADC values in lesions with ICC values of 0.79 and 0.92, respectively. Intraobserver agreement for ADC values in lesions assessed with EPI- versus HASTE-DWI techniques was low, with ICC values of 0.31 and 0.42, respectively. Significant interobserver disagreement concerning detection was only seen with HASTE-DWI, and none of the DWI techniques showed significant interobserver disagreements regarding delineation. EPI-DWI was more prone to susceptibility artifacts than HASTE-DWI: Ninety-one percent of primary tumors and 16% of lymph nodes were affected by susceptibility artifacts on pretreatment EPI-DWI, whereas these artifacts were not seen on HASTE-DWI. CONCLUSIONS: Primary tumors and lymph nodes are more easily visualized on EPI-DWI compared with HASTE-DWI. EPI-DWI has geometric distortion, however, which has a negative effect on interobserver agreement of ADC values.

Single-shot turbo spin-echo diffusion-weighted imaging for retinoblastoma: initial experience.

BACKGROUND AND PURPOSE: Retinoblastoma may exhibit variable hyperintensities on DWI, resulting in different values in the ADC maps, depending on their histology and cellularity. However, EP-based DWI has susceptibility artifacts and image distortions, which make DWI of the orbit a challenging technique. The aim of this study was to investigate the feasibility of single-shot turbo spin-echo (HASTE) DWI in the evaluation of children with retinoblastoma and to assess the value of ADC maps in differentiating viable and necrotic tumor tissue. MATERIALS AND METHODS: Two radiologists assessed conventional MR images, DWI, and ADC maps of 17 patients with retinoblastoma (n = 17 eyes). Non-EP DWI was performed by using a HASTE sequence with b-values of 0 and 1000 s/mm(2). ADC values were measured for enhancing and nonenhancing tumor tissue. ADC maps were compared with histopathologic findings regarding tumor differentiation and viability. RESULTS: On DWI, vital tumor tissue showed hyperintensity with negligible intensity of surrounding vitreous. The difference in mean (range) ADC values between enhancing (1.03 [0.72-1.22] × 10(-3) mm(2) s(-1)) and nonenhancing (1.47 [0.99-1.80] × 10(-3) mm(2) s(-1)) parts of retinoblastoma was statistically significant (P < .0005). Nonenhancing tumor parts showed a significantly lower ADC compared with vitreous (2.67 [2.24-3.20]×10(-3) mm(2) s(-1)) (P < .0005) and subretinal fluid (2.20 [1.76-2.96] × 10(-3) mm(2) s(-1)) (P < .0005). Histopathologically, low ADC values (enhancing tumor part) correlated to viable tumor tissue, whereas intermediate ADC values (nonenhancing tumor parts) correlated to necrotic tumor tissue. CONCLUSIONS: HASTE DWI allowed adequate characterization of retinoblastoma, and ADC is a helpful tool to differentiate viable and necrotic tumor tissue and might be valuable in monitoring the response to eye-preserving therapies.

Quantitative MR imaging and spectroscopy in congenital cytomegalovirus infection and periventricular leukomalacia suggests a comparable neuropathological substrate of the cerebral white matter lesions.

Congenital CYTOMEGALOVIRUS (CMV) infection and periventricular leukomalacia (PVL) both lead to static cerebral white matter lesions. In contrast to PVL, the neuropathologicAL substrate of these lesions in congenital CMV is not clear. By comparing changes in quantitative magnetic resonance (MR) parameters and MR spectroscopy metabolite concentrations we wanted to determine whether the nature of the white matter pathology in congenital CMV infection could be similar to the known pathology of PVL. Diffusion parameters, apparent diffusion coefficient (ADC) and fractional anisotropy (FA), magnetization transfer ratio (MTR) and MR spectroscopy concentrations were studied in white matter lesions in five patients with a congenital CMV infection and six patients with PVL. In both groups ADC values were increased, FA and MTR values were reduced, concentrations of total N-acetylaspartate and choline-containing compounds were reduced; and MYO-inositol concentrations were slightly increased. No differences were found between the two groups, suggesting that the pathology of the white matter lesions in congenital CMV infections is similar to that of PVL and also characterized by axonal losses, lack of myelin deposition due to oligodendrocytic losses, and astrogliosis. Congenital CMV infection and PVL affect the cerebral white matter in the same developmental period when immature oligodendrocytes are particularly vulnerable.

MR spectroscopy and serial magnetic resonance imaging in a patient with mitochondrial cystic leukoencephalopathy due to complex I deficiency and NDUFV1 mutations and mild clinical course.

We present clinical, magnetic resonance imaging and MR spectroscopic findings of a female patient, first admitted at the age of 9 months for regression of motor milestones and signs of mild spastic diplegia. Magnetic resonance imaging (MRI) demonstrated periventricular white matter abnormalities with sparing of the subcortical white matter. Subsequent MRIs, performed at the ages of 13 and 16 months, demonstrated progression of the white matter changes, progressive white matter rarefaction and cystic degeneration, and additional involvement of the corpus callosum; only the subcortical white matter remained spared. Proton MR spectroscopy revealed lactate elevation in the white matter. Blood lactate and lactate/pyruvate ratio were mildly elevated. Subsequent analysis of mitochondrial function in muscle tissue showed decreases in substrate oxidation and in ATP and CrP production rates. Complex I activity was seriously decreased, whereas mild decreases of complex II and IV activities were also noted. Analysis of the NDUFV1 gene revealed compound heterozygosity for two point mutations, each of them carried by one parent. The further clinical course of the patient was uphill; she slowly regained all previously lost motor milestones. In conclusion, diffuse white matter changes on MRI are compatible with mitochondrial encephalopathy and not necessarily associated with a severe clinical course.

Has the degree of contrast enhancement with MR imaging in laryngeal carcinoma added value to anatomic parameters regarding prediction of response to radiation therapy?

BACKGROUND AND PURPOSE: Our aim was to retrospectively investigate the prognostic significance of the degree of contrast enhancement in tumors and its additional value in previously considered MR imaging parameters with regard to local control of laryngeal cancer treated with radiation therapy (RT) alone. MATERIALS AND METHODS: Pretreatment MR images of 64 consecutive patients (54 men and 10 women, 43-80 years of age) with supraglottic and glottic cancer were retrospectively reviewed on clinical and previously considered MR imaging parameters such as tumor involvement of specific laryngeal anatomic subsites, including laryngeal cartilages, tumor volume, extralaryngeal tumor spread, and, in addition, the degree of contrast enhancement. Clinical and MR imaging parameters were associated with regard to local control at 2 years by using the Cox regression model. "Local control" was defined as absence of primary tumor recurrence. RESULTS: When using a threshold of the mean average contrast enhancement of 77%, the 2-year local control rate in the groups of patients with a degree of enhancement below and above this threshold was 57% and 70%, respectively (P=.3). Enhancement of tumor tissue in pre-epiglottic space (PES) was low, most probably due to its adipose tissue and poor vascular content, whereas tumor tissue involving paraglottic space (PGS) did enhance. Results of multivariate analysis indicated that the degree of contrast enhancement yielded the prognostic information (P=.07) with 2 independent prognostic factors: primary tumor volume (P=.007) and subglottic extension (P=.002) with regard to local control. Using these previously mentioned 3 MR imaging parameters as potential risk factors, we defined 4 categories, resulting in the following local control rates respectively: 90% for the group without risk factors, 73% for the group with 1, 60% for the group with 2, and finally 0% for the group with 3 risk factors, which was significantly lower than the rates in previous risk groups (P < .001). CONCLUSION: PES has a lower degree of contrast enhancement than the PGS and may correlate with the worse outcome. Including a low degree of contrast enhancement as a parameter to primary tumor volume and subglottic extension may increase the predictive value of MR imaging for local outcome and may be helpful to identify a subset of patients whose tumors all recurred locally within 2 years after primary RT.

Quantitative proton magnetic resonance spectroscopy of children with adrenoleukodystrophy before and after hematopoietic stem cell transplantation.

About 35-40 % of boys with X-linked adrenoleukodystrophy (ALD) develop a rapidly progressive cerebral form which leads to severe neurologic disability and death within 3-5 years after onset of clinical symptoms. Because previous proton magnetic resonance spectroscopy (MRS) studies of ALD identified metabolite patterns characteristic of demyelination, gliosis, and neuroaxonal loss, this work tested the hypothesis that MRS--apart from indicating disease progression--provides criteria for the outcome after hematopoietic stem cell transplantation (HSCT) which has been promising at an early stage of the active disease. Follow-up quantitative proton MRS was performed in frontal and occipital white matter of ALD patients (n = 12) before and up to 5 years after HSCT. The observed metabolite alterations were retrospectively correlated with the clinical outcome representing either a stable condition (n = 5), a further deterioration (n = 5), or death (n = 2). While disease progression of patients before HSCT was mainly characterized by a further increase of elevated choline-containing compounds (Cho) as an indicator of active demyelination, a positive outcome after HSCT was correlated with high N-acetylaspartate (tNAA) levels in affected white matter before HSCT yielding positive and negative predictive values for tNAA of 80 %. Although to be confirmed in a larger cohort of patients, the present findings suggest the preservation of neuroaxonal integrity as a prerequisite for an arrested course. Conversely, the combination of increased Cho with markedly reduced tNAA before HSCT apparently reflects a degree of tissue degeneration which precludes a successful therapeutic intervention.

Regional age dependence of human brain metabolites from infancy to adulthood as detected by quantitative localized proton MRS.

Regional changes of metabolite concentrations during human brain development were assessed by quantitative localized proton magnetic resonance spectroscopy in vivo. Apart from measurements in young healthy adults, the study was based on regional spectra from 97 children who were either healthy or suffered from mental retardation, movement disorders, epilepsies, neoplasm, or vascular malformation. Metabolite quantitation focused on cortical gray and white matter, cerebellum, thalamus, and basal ganglia in six age groups from infancy to adulthood. During infancy and childhood, the concentration of the neuroaxonally located N-acetylasparate increased in gray matter, cerebellum, and thalamus, whereas a constant level was detected in white matter. These findings are in line with regional differences in the formation of synaptic connections during early development and suggest a role of N-acetylaspartate as a marker of functioning neuroaxonal tissue rather than of the mere presence of nerve cells. This view is further supported by high concentrations of taurine in gray matter and cerebellum during infancy, because taurine is also believed to be involved in the process of synapse formation. Remarkably, in basal ganglia both N-acetylaspartate and taurine remain constant at relatively high concentrations. Other metabolite changes during maturation include increases of N-acetylaspartylglutamate, especially in thalamus and white matter, and a decrease of glutamine in white matter. Despite regional differences and some small changes during the first year of life, the concentrations of creatine, phosphocreatine, choline-containing compounds, myoinositol, and glutamate remain constant afterward. The creatine to phosphocreatine concentration ratio yields 2:1 throughout the human brain irrespective of region or age. The observed increase of the proton resonance line-width with age is most pronounced in basal ganglia and corresponds to the age-related and tissue-dependent increase of brain iron.

Neuronal damage in T1-hypointense multiple sclerosis lesions demonstrated in vivo using proton magnetic resonance spectroscopy.

Hypointense T1 lesions in multiple sclerosis patients correlate with axonal loss at autopsy and biopsy. We evaluated the chemical substrate of hypointense T1 lesions by using in vivo proton magnetic resonance spectroscopy, and analyzed the spectroscopic correlate of increased T1-relaxation time measurements. Localized proton magnetic resonance spectroscopy and T1-relaxation time measurements were performed in lesions, selected on T1-weighted spin-echo magnetic resonance images according to degree of hypointensity, in normal appearing white matter (NAWM) and in normal white matter of controls. In NAWM, prolongation of T1-relaxation time and a decrease in N-acetylaspartate (NAA) were present, compared with normal white matter. Severely hypointense lesions showed a lower concentration of NAA and creatine compared with NAWM and a lower concentration of NAA compared with isointense to mildly hypointense lesions. NAA concentration correlated with degree of hypointensity of lesions and with T1-relaxation time within the spectroscopic voxel. Our results provide the first in vivo evidence of axonal damage in severely hypointense T1 lesions in multiple sclerosis patients. T1-relaxation time correlates with the concentration of NAA in both multiple sclerosis lesions and NAWM, indicating that this parameter deserves further evaluation to monitor disease progression.

Quantitative proton magnetic resonance spectroscopy of childhood adrenoleukodystrophy.

Cerebral metabolic disturbances in patients with childhood adrenoleukodystrophy (ALD) were assessed by quantitative localized proton MRS. Patient monitoring by follow-up MRS studies served to identify putative markers for disease onset and progression. Whereas normal-appearing white matter of neurologically asymptomatic patients is characterized by slightly elevated concentrations of choline-containing compounds (Cho), an increase of both Cho and myo-inositol (Ins) seems to indicate the onset of demyelination. Markedly elevated concentrations of Cho, Ins, and glutamine in affected white matter reflect active demyelination and glial proliferation. A simultaneous reduction of the concentrations of N-acetylaspartate and glutamate is consistent with neuronal damage or loss. The observation of elevated lactate is in line with inflammation and/or macrophage infiltration. The more severe metabolic disturbances in cerebral ALD correspond to progressive demyelination, neuroaxonal loss and gliosis leading to clinical deterioration and eventually death. The detection of MRS abnormalities before the onset of neurological symptoms may help in the selection of patients for bone marrow transplantation (BMT). Stabilization and partial reversal of metabolic abnormalities is demonstrated in a patient after BMT.

Proton magnetic resonance spectroscopy of linear nevus sebaceus syndrome.

Cerebral metabolites of a patient with linear nevus sebaceus syndrome and hemimegalencephaly were determined at 18 and 30 months of age by localized proton magnetic resonance spectroscopy. Clinically, the patient suffered from hemiparesis and epileptic seizures. At 18 months of age, spectroscopy of the enlarged hemisphere revealed decreased N-acetylaspartate mainly in parietal white matter relative to the unaffected hemisphere. One year later, white matter studies indicated both reduced N-acetylaspartate and elevated myoinositol. In insular gray matter the previously normal concentrations of creatine, choline-containing compounds, myoinositol, and glutamine were increased. The findings are consistent with mild neuroaxonal loss or damage (white matter) and glial proliferation (cortical gray and white matter) of the affected hemisphere. The metabolic disturbances indicate disease progression but are less pronounced than in older patients with hemimegalencephaly.

Cystic leukoencephalopathy in a megalencephalic child: clinical and magnetic resonance imaging/magnetic resonance spectroscopy findings.

A neurodegenerative disorder characterized by megalencephaly since early infancy and slowly progressive symptoms of cerebellar, pyramidal, and extrapyramidal dysfunction, pseudobulbar signs, and epilepsy was detected in an 8-year-old girl with severe neuromotor handicap but preservation of mental and sensory functions. Cranial computed tomography and magnetic resonance imaging revealed brain swelling as well as severe abnormalities of frontal, temporal, and parietal white matter, with an extended cystlike appearance isointense to cerebrospinal fluid. Localized proton magnetic resonance spectroscopy of affected cystic white matter showed a loss of all metabolites, in accordance with a complete disintegration of neuroaxonal and glial tissue. This case is likely a severe variant of a recently described megalencephalic leukoencephalopathy with swelling and discrepantly mild clinical course.