Comparative evaluation of brain neurometabolites and DTI indices following whole body and cranial irradiation: a magnetic resonance imaging and spectroscopy study.

Understanding early differential response of brain during whole body radiation or cranial radiation exposure is of significant importance for better injury management during accidental or intentional exposure to ionizing radiation. We investigated the early microstructural and metabolic profiles using in vivo diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy ((1)H MRS) following whole body and cranial radiation exposure of 8 Gy in mice using a 7.0 T animal MRI system and compared profiles with sham controls at days 1, 3, 5 and 10 post irradiation. A significant decrease in fractional anisotropy (FA) values was found in hippocampus, thalamic and hypothalamic regions (p < 0.05) in both whole body and cranial irradiated groups compared with controls, suggesting radiation induced reactive astrogliosis or neuroinflammatory response. In animals exposed to whole body radiation, FA was significantly decreased in some additional brain regions such as sensory motor cortex and corpus callosum in comparison with cranial irradiation groups and controls. Changes in FA were observed till day 10 post irradiation in both the groups. However, MRS study from hippocampus revealed changes only in the whole body radiation dose group. Significant reduction in the ratios of the metabolites myoinositol (mI, p = 0.02) and taurine (tau, p = 0.03) to total creatine were observed, and these metabolic alterations persisted till day 10 post irradiation. To the best of our knowledge this study has for the first time documented a comparative account of microstructural and metabolic aspects of whole body and cranial radiation induced early brain injury using in vivo MRI. Overall our findings suggest differential response at microstructure and metabolite levels following cranial or whole body radiation exposure.

T1-weighted dynamic contrast-enhanced MR evaluation of different stages of neurocysticercosis and its relationship with serum MMP-9 expression.

BACKGROUND AND PURPOSE: Epileptogenesis in NCC is associated with perilesional inflammation and disruption in BBB. We quantified BBB in different stages of NCC by using DCE-MR imaging to look for the differences in perfusion indices and to correlate these indices with serum MMP-9 expression. MATERIALS AND METHODS: DCE-MR imaging along with conventional MR imaging was performed in 57 single cysticercous brain lesions to quantify the kep, K(trans), and ve around the lesions, which were in different stages of evolution. There were 6 lesions in the vesicular stage and 17 lesions each in the colloidal, granular-nodular, and calcified stages. Serum MMP-9 was quantified from all patients, whereas perfusion indices were quantified from all stages except for the vesicular stage. RESULTS: We observed significant differences among the 3 stages of NCC in serum MMP-9 expression as well as DCE-derived kep values. In addition, kep showed a strongly significant positive correlation with MMP-9 expression when modeled with the individual stage of the disease as well as with all stages when pooled together. Other DCE-derived hemodynamic and pharmacokinetic parameters showed inconsistent differences with each stage of the disease. The correlation of DCE-derived parameters with serum MMP-9 expression and edema volume also showed inconsistency with the stage of the disease. CONCLUSIONS: We conclude that kep correlates best with serum MMP-9 expression among the pharmacokinetic indices and most closely represents the degree of BBB breakdown, which is highest in the colloidal stage and lowest in the calcified stage. kep may be used as a noninvasive image biomarker of BBB breakdown in different stages of NCC.

An exploratory study into the role of dynamic contrast-enhanced (DCE) MRI metrics as predictors of response in head and neck cancers.

AIM: To assess the efficacy of dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) in prediction of the response to treatment in patients with head and neck cancers (HNCs). METHODS AND MATERIALS: Twenty-one patients with advanced HNC, suitable for concurrent chemoradiotherapy underwent DCE MRI, for the quantification of blood flow (BF) and volume (BV). All the patients received radical doses of conventionally fractionated radiotherapy up to a dose of 70 Gy along with concurrent weekly cisplatin. RESULTS: The values of BV and BF were higher in complete responders as compared to partial responders at primary as well as nodes. Both BF and BV were found to be significantly higher in patients with high T-stage as compared to patients with lower T-stage. CONCLUSIONS: DCE metrics can be used as a predictor of response to treatment in locally advanced HNCs after validation of these observations in a larger number of patients.

Understanding epileptogenesis in calcified neurocysticercosis with perfusion MRI.

OBJECTIVES: Calcified cysticercus larva with perilesional abnormality is thought to be responsible for seizures in patients with neurocysticercosis (NCC). However, it is not well understood why some calcified cysts are associated with seizures even without perilesional abnormality. METHODS: The study group consists of 30 subjects from an ongoing survey for disease burden estimation of a swine farming community who had a single calcified lesion without any perilesional abnormality with or without presentation of seizures. Each group consisted of 15 patients with calcified cysts and was labeled as asymptomatic and symptomatic. We performed dynamic contrast-enhanced (DCE) MRI on all these subjects and determined serum matrix metalloproteinase-9 (MMP-9) levels and MMP-9 gene polymorphisms. RESULTS: DCE-MRI-derived rate transfer constant (k(ep)) and serum MMP-9 levels showed significant differences between symptomatic and asymptomatic subjects. We observed an increase in the MMP-9 levels, k(ep), and the volume transfer coefficient (k(trans)) in these lesions. We also observed a significant increase in MMP-9 (R279Q) gene polymorphism in symptomatic subjects compared with asymptomatic and control subjects. CONCLUSIONS: Perilesional inflammation, which varies from symptomatic to asymptomatic subjects, can be quantified using DCE-MRI in calcified cysticercosis and may help distinguish these 2 groups with similar imaging findings. The observed increase in k(ep) with serum MMP-9 levels suggests that the former may serve as a biomarker of MMP-9 levels in these subjects. The significant MMP-9 (R279Q) gene polymorphism in symptomatic subjects might explain the differences in the observed DCE-MRI indices between symptomatic and asymptomatic subjects.

Apparent diffusion coefficient with higher b-value correlates better with viable cell count quantified from the cavity of brain abscess.

BACKGROUND AND PURPOSE: DWI by using higher b-values provides tissue diffusivity with less T2 shinethrough effect. VCD in the abscess cavity correlates with ADC values. The purpose of this study was to investigate which b-value-derived ADC correlates better with VCD. MATERIALS AND METHODS: Thirty patients with brain abscess underwent conventional MR imaging and DWI with b = 1000, 2000, and 3000 s/mm(2) on a 3T MR imaging scanner. ADC values were quantified by placing regions of interest inside the abscess cavity in all sections where the lesion was apparent on coregistered ADC maps derived from different b-values. VCD was measured on pus aspirated. RESULTS: An increase in b-value was associated with a decrease in ADC values in normal parenchyma as well as in the abscess cavity. The most significant negative correlation of VCD was observed with b = 3000 s/mm(2) (r = -0.98, P = .01). CONCLUSIONS: VCD in the abscess cavity can be best assessed at b = 3000 s/mm(2) secondary to the reduction in the T2 shinethrough effect. DWI with b = 3000 s/mm(2) is of promising value in the assessment of the therapeutic response of brain abscess.

Correlation of quantitative diffusion tensor tractography with clinical grades of subacute sclerosing panencephalitis.

BACKGROUND AND PURPOSE: SSPE is a persistent infection of the central nervous system caused by the measles virus. The correlation between the clinical staging and conventional MR imaging is usually poor. The purpose of this study was to determine whether tract-specific DTI measures in the major white mater tracts correlate with clinical grades as defined by the Jabbour classification for SSPE. MATERIALS AND METHODS: Quantitative DTT was performed on 20 patients with SSPE (mean age, 9 years) and 14 age- and sex-matched controls. All patients were graded on the basis of the Jabbour classification into grade II (n=9), grade III (n=6), and grade IV (n=5) SSPE. The major white matter tracts quantified included the CC, SLF, ILF, CST, CNG, SCP, MCP, ICP, ATR, STR, and PTR. RESULTS: Although a successive decrease in mean FA values was observed in all the fiber tracts except for the SCP and ICP, moving from controls to grade IV, a significant inverse correlation between clinical grade and mean FA values was observed only in the splenium (r=-0.908, P<.001), CST (r=-0.663, P=.013), SLF (r=-0.533, P=.050), ILF (r=-0.776, P=.001), STR (r=-0.538, P=.047), and PTR (r=-0.686, P=.035) fibers. No significant correlation of mean MD values from these white matter tracts was observed with clinical grades of the disease. CONCLUSIONS: We conclude that the grade of encephalopathy correlates inversely with the tract-specific mean FA values. This information may be valuable in studying the disease progression with time and in assessing the therapeutic response in the future.

Brain MR imaging and 1H-MR spectroscopy changes in patients with extrahepatic portal vein obstruction from early childhood to adulthood.

BACKGROUND AND PURPOSE: MR imaging and (1)H-MR spectroscopy changes are well reported in cirrhotic patients, whereas they are inadequately reported in EHPVO. The aim of this study was to investigate age-related changes in brain MR imaging and metabolite profile in EHPVO with and without MHE and to explore any correlation of imaging and (1)H-MR spectroscopy parameters with blood ammonia. MATERIALS AND METHODS: Sixty-three patients with EHPVO (children, 7-12 years [n = 22], adolescents, 13-18 years [n = 15] and adults, 19-41 years [n = 26]) and 47 healthy age/sex-matched volunteers were studied. Neuropsychological tests, MR imaging, (1)H-MR spectroscopy, and blood ammonia estimation were performed in all subjects. RESULTS: Of 63 EHPVO patients, 25 (40%) who had MHE showed significantly increased MD, Glx, and blood ammonia in all 3 age groups; however, myo-inositol was significantly lower only in adults when compared with controls. MD positively correlated with blood ammonia and Glx in all age groups. Brain choline levels were normal in all patients with different age groups. CONCLUSIONS: Increases in brain MD, Glx, and blood ammonia were associated with MHE in all age groups. Normal brain choline in EHPVO signifies healthy liver and may serve as a diagnostic marker for its differentiation from cirrhosis-induced encephalopathy. Significant decrease of myo-inositol in adults is probably due to cellular osmoregulation secondary to long-standing hyperammonemia.

Diffusion tensor MR imaging in children with pantothenate kinase-associated neurodegeneration with brain iron accumulation and their siblings.

BACKGROUND AND PURPOSE: It has been reported that iron concentration influences DTI metrics in deep gray matter nuclei. We hypothesized that increased FA in the deep gray nuclei may indicate abnormal iron accumulation in patients with PKAN and their siblings. MATERIALS AND METHODS: Seven patients with the characteristic "eye-of-the-tiger sign," their 5 siblings, and 5 age-matched controls were prospectively studied. One-way ANOVA with Bonferroni post hoc multiple comparisons was used to compare DTI metrics (FA and MD) among subject groups in the putamen, CN, GP, SN, and ALIC. In addition, hypointense and hyperintense regions of the eye-of-the-tiger sign were segmented, and their DTI metrics were compared. In the patient group, the values of DTI metrics in hypointense regions were also compared with those of the ALIC. RESULTS: A significant increase in FA values of the GP and SN from controls to the patient group to siblings was observed. In the GP, MD values were significantly higher in patients compared with controls and siblings. The patients showed significantly increased FA with decreased MD in hypointense compared with hyperintense regions of the eye-of-the-tiger sign. No difference in FA values were observed between the ALIC and hypointense regions of the eye-of-the-tiger sign in patients. CONCLUSIONS: High FA values in siblings of patients with PKAN suggest the presence of abnormal iron in deep gray matter nuclei, even in the absence of its demonstration on T2*-weighted GRE.

In vivo demonstration of neuroinflammatory molecule expression in brain abscess with diffusion tensor imaging.

BACKGROUND AND PURPOSE: Neuroinflammatory molecules, including tumor necrosis factor-alpha, interleukin1-beta, lymphocyte function associated molecule-1, and intercellular cell adhesion molecule-1 contribute to the development of brain abscess. We hypothesized that the high fractional anisotropy (FA) in the brain abscess cavity reflects the upregulation of these neuroinflammatory molecules. MATERIALS AND METHODS: Diffusion tensor imaging (DTI) was performed in 24 patients with brain abscess and Staphylococcus aureus-treated as well as nontreated Jurket cell lines (at 4 time points: 1, 24, 48, and 72 hours). Neuroinflammatory molecules were quantified from the brain abscess cavity aspirate of the patients as well as from the heat-killed S aureus-treated and nontreated cell lines and correlated with DTI measures. RESULTS: The DTI-derived FA strongly correlated with the presence of neuroinflammatory molecules in the pus as well as in S aureus-treated cell lines; no such correlation was observed in nontreated cell lines. CONCLUSIONS: These data indicate that neuroinflammatory molecules confer high diffusion anisotropy inside the brain abscess cavity. We propose that increased FA reflects upregulated inflammatory response in brain abscess.

Can we differentiate true white matter fibers from pseudofibers inside a brain abscess cavity using geometrical diffusion tensor imaging metrics?

High fractional anisotropy (FA) usually reflects the orientation and integrity of white matter (WM) fibers. Other regions of increased FA have been described, such as brain abscesses, developing cortex, and areas of hemorrhage. It may not be possible to differentiate true fibers from the pseudofibers found inside an abscess cavity on the basis of FA and mean diffusivity (MD). The aim of this study was to differentiate true WM fibers from pseudo WM tracts inside the abscess cavity using geometrical diffusion tensor imaging metrics [linear anisotropy (CL), planar anisotropy (CP), and spherical anisotropy (CS)]. Diffusion tensor imaging was performed in 42 patients with brain abscess and 10 age/sex-matched controls. Automated segmentation using Java-based software divided the abscess cavity into two sub-regions with FA < 0.20 and FA > or = 0.20. Quantitation was carried out on the sub-regions of the abscess cavity with FA > or = 0.20. In healthy controls, regions of interest were placed on the corpus callosum, posterior limb of the internal capsule, and periventricular and subcortical WM. Significantly increased CP values were observed inside the abscess cavity compared with various normal WM regions. Significantly increased FA and CL values were observed in the abscess cavity compared with subcortical WM only. However decreased FA and CL values were observed in the cavity compared with the corpus callosum, posterior limb of the internal capsule, and periventricular WM. The 95% confidence intervals of means for the abscess cavity were well separated from those for WM in the case of CL and CP; however, they overlapped in the case of FA, MD, and CS. High CP with low CL inside the abscess cavity suggests that the shape of the diffusion tensor is predominantly planar, whereas it is linear in WM tracts. These geometrical indices may have advantages over FA for differentiating true from pseudo WM tracts inside the abscess cavity.

Clinical implications of increased fractional anisotropy in meningitis associated with brain abscess.

AIM: To look for the clinical implications of increased cortical fractional anisotropy (FA) in meningitis patients associated with brain abscess. MATERIAL AND METHODS: Diffusion tensor imaging was performed in 10 patients of meningitis associated with brain abscess and 10 controls. The region of interest analysis was performed to calculate FA and mean diffusivity values from the abscess cavity and cortical regions of patients (enhancing and nonenhancing meninges on postcontrast T1-weighted images) and controls. RESULTS: Significantly increased FA values with no change in mean diffusivity values were found in enhancing (FA = 0.113 +/- 0.023, P = 0.000) as well as nonenhancing (FA = 0.085 +/- 0.009, P = 0.000) cortical region of patients compared with controls (FA = 0.067 +/- 0.010). CONCLUSIONS: Increased FA values in the enhancing as well as nonenhancing cortical regions suggest diffuse inflammatory activity in the pia-arachnoid in meningitis patients. It also suggests that FA may be a better indicator of active and diffuse meningeal inflammation than postcontrast T1-weighted images.

Assessment of white matter damage in subacute sclerosing panencephalitis using quantitative diffusion tensor MR imaging.

BACKGROUND AND PURPOSE: Subacute sclerosing panencephalitis (SSPE), a rare progressive degenerative disease, is caused by persistent infection with a defective measles virus. The correlation between the clinical staging and MR imaging is usually poor. The aim of the study was to investigate the role of diffusion tensor imaging (DTI) in the early detection of white matter damage in SSPE in the presence of normal findings on conventional imaging. METHODS: DTI was performed in 21 patients in stage II SSPE and 10 age/sex-matched healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated in the periventricular white matter, corpus callosum, and posterior limb of the internal capsule in patients with normal and abnormal findings on conventional imaging as well as healthy controls. RESULTS: The patients were grouped into those with normal (n = 11) and abnormal (n = 10) findings on conventional imaging for the purpose of quantitative DTI analysis. Abnormal- and normal-appearing white matter on T2-weighted images showed significantly decreased FA values in all the regions compared with those in healthy controls. MD values were significantly increased in the periventricular white matter region of the frontal and parietooccipital lobe in patients with normal as well as abnormal findings on conventional imaging compared with those in healthy controls. CONCLUSION: DTI detects early white matter abnormalities that may have significant therapeutic implication, even in the presence of normal findings on conventional imaging, in patients with SSPE.

Demonstration of scolex in calcified cysticercus lesion using gradient echo with or without corrected phase imaging and its clinical implications.

AIM: This study was performed to determine the magnetic resonance imaging (MRI) sequence that was best suited to demonstrate the scolex in a calcified lesion and to seek the explanation for the appearance of a negative phase in a calcified scolex on corrected gradient refocused echo (GRE) phase imaging. MATERIALS AND METHODS: Forty-nine patients with single/multiple computed tomography (CT) documented homogeneous calcified lesions and/or calcified scolices in cysts were studied with conventional spin echo and corrected GRE phase imaging. Calcium and different paramagnetic substances from cysticerci scolices of a sample of infected swine muscle were quantified. RESULTS: The scolex could be demonstrated in 29/39 patients with single calcified lesion. GRE imaging with an echo time of 35ms was the only sequence that demonstrated scolex in all these 29 cases. 15/29 patients with a single calcified lesion, in all 10 patients with multiple calcified lesions and infected swine muscle with multiple cysts and calcified scolex, corrected GRE phase imaging showed negative phase in all these scolices. Estimation of minerals from the calcified scolices from the swine muscle showed by spectroscopic techniques 41.2% of the total mineral contents as paramagnetic substances. CONCLUSION: We conclude that GRE imaging is the imaging method of choice for demonstration of the scolex in a CT calcified lesion. The negative phase on corrected GRE phase imaging is due to the presence of large amount of paramagnetic substances.

Multiparametric quantitation of the perilesional region in patients with healed or healing solitary cysticercus granuloma.

The purpose of this study was to compute T2 values and magnetization transfer (MT) ratios in the perilesional region of healing and healed cysticercus granulomas to determine if there are T2 abnormalities not apparent on conventional T2-weighted imaging and to determine the relationship between seizure control and the quantitative measures. Sixty-three patients were studied. T2 values and MT ratios were computed for the perilesional region and were compared with measurements from the contralateral normal-appearing region. A significantly increased T2 value was found for the perilesional region compared to the corresponding contralateral region despite the absence of qualitative abnormality on conventional T2-weighted magnetic resonance imaging. For patients showing normal-appearing perilesional regions on MT imaging, there was no significant difference in T2 and MT ratios between the perilesional and the normal contralateral regions. There was a statistically significant inverse correlation between perilesional T2 values and MT ratios, suggesting each was associated with perilesional gliosis. The study illustrates that quantitative evaluation of MT ratios and T2 augments the qualitative visual assessment of the perilesional region in healing or healed cysticercus granulomas.