Enrico De Vita

Mural Inflammation in Crohn Disease: Location-Matched Histologic Validation of MR Imaging Features

PURPOSE To validate proposed magnetic resonance (MR) imaging features of Crohn disease activity against a histopathologic reference. MATERIALS AND METHODS Ethical permission was given by the University College London hospital ethics committee, and informed written consent was obtained from all participants. Preoperative MR imaging was performed in 18 consecutive patients with Crohn disease undergoing elective small-bowel resection. The Harvey-Bradshaw index, the C-reactive protein level, and disease chronicity were recorded. The resected bowel was retrospectively identified at preoperative MR imaging, and wall thickness, mural and lymph node/cerebrospinal fluid (CSF) signal intensity ratios on T2-weighted fat-saturated images, gadolinium-based contrast material uptake, enhancement pattern, and mesenteric signal intensity on T2-weighted fat-saturated images were recorded. Precise histologic matching was achieved by imaging the ex vivo surgical specimens. Histopathologic grading of acute inflammation with the acute inflammatory score (AIS) (on the basis of mucosal ulceration, edema, and quantity and depth of neutrophilic infiltration) and the degree of fibrostenosis was performed at each site, and results were compared with MR imaging features. Data were analyzed by using linear regression with robust standard errors of the estimate. RESULTS AIS was positively correlated with mural thickness and mural/CSF signal intensity ratio on T2-weighted fat-saturated images (P < .001 and P = .003, respectively) but not with mural enhancement at 30 and 70 seconds (P = .50 and P = .73, respectively). AIS was higher with layered mural enhancement (P < .001), a pattern also commonly associated with coexisting fibrostenosis (75%). Mural/CSF signal intensity ratio on T2-weighted fat-saturated images was higher in histologically edematous bowel than in nonedematous bowel (P = .04). There was no correlation between any lymph node characteristic and AIS. CONCLUSION Increasing mural thickness, high mural signal intensity on T2-weighted fat-saturated images, and a layered pattern of enhancement reflect histologic features of acute small-bowel inflammation in Crohn disease.

Voxel-based cortical thickness measurements in MRI

The thickness of the cerebral cortex can provide valuable information about normal and abnormal neuroanatomy. High resolution MRI together with powerful image processing techniques has made it possible to perform these measurements automatically over the whole brain. Here we present a method for automatically generating voxel-based cortical thickness (VBCT) maps. This technique results in maps where each voxel in the grey matter is assigned a thickness value. Sub-voxel measurements of thickness are possible using sub-sampling and interpolation of the image information. The method is applied to repeated MRI scans of a single subject from two MRI scanners to demonstrate its robustness and reproducibility. A simulated data set is used to show that small focal differences in thickness between two groups of subjects can be detected. We propose that the analysis of VBCT maps can provide results that are complementary to other anatomical analyses such as voxel-based morphometry.

Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: a cross-sectional analysis

BACKGROUND Frontotemporal dementia is a highly heritable neurodegenerative disorder. In about a third of patients, the disease is caused by autosomal dominant genetic mutations usually in one of three genes: progranulin (GRN), microtubule-associated protein tau (MAPT), or chromosome 9 open reading frame 72 (C9orf72). Findings from studies of other genetic dementias have shown neuroimaging and cognitive changes before symptoms onset, and we aimed to identify whether such changes could be shown in frontotemporal dementia. METHODS We recruited participants to this multicentre study who either were known carriers of a pathogenic mutation in GRN, MAPT, or C9orf72, or were at risk of carrying a mutation because a first-degree relative was a known symptomatic carrier. We calculated time to expected onset as the difference between age at assessment and mean age at onset within the family. Participants underwent a standardised clinical assessment and neuropsychological battery. We did MRI and generated cortical and subcortical volumes using a parcellation of the volumetric T1-weighted scan. We used linear mixed-effects models to examine whether the association of neuropsychology and imaging measures with time to expected onset of symptoms differed between mutation carriers and non-carriers. FINDINGS Between Jan 30, 2012, and Sept 15, 2013, we recruited participants from 11 research sites in the UK, Italy, the Netherlands, Sweden, and Canada. We analysed data from 220 participants: 118 mutation carriers (40 symptomatic and 78 asymptomatic) and 102 non-carriers. For neuropsychology measures, we noted the earliest significant differences between mutation carriers and non-carriers 5 years before expected onset, when differences were significant for all measures except for tests of immediate recall and verbal fluency. We noted the largest Z score differences between carriers and non-carriers 5 years before expected onset in tests of naming (Boston Naming Test -0·7; SE 0·3) and executive function (Trail Making Test Part B, Digit Span backwards, and Digit Symbol Task, all -0·5, SE 0·2). For imaging measures, we noted differences earliest for the insula (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume was 0·80% in mutation carriers and 0·84% in non-carriers; difference -0·04, SE 0·02) followed by the temporal lobe (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume 8·1% in mutation carriers and 8·3% in non-carriers; difference -0·2, SE 0·1). INTERPRETATION Structural imaging and cognitive changes can be identified 5-10 years before expected onset of symptoms in asymptomatic adults at risk of genetic frontotemporal dementia. These findings could help to define biomarkers that can stage presymptomatic disease and track disease progression, which will be important for future therapeutic trials. FUNDING Centres of Excellence in Neurodegeneration.

Mural Crohn Disease: Correlation of Dynamic Contrast-enhanced MR Imaging Findings with Angiogenesis and Inflammation at Histologic Examination—Pilot Study

PURPOSE To determine mural perfusion dynamics in Crohn disease by using dynamic contrast material-enhanced magnetic resonance (MR) imaging and to correlate these with histopathologic markers of inflammation and angiogenesis. MATERIALS AND METHODS Ethical permission was given by the University College London Hospital ethics committee, and informed consent was obtained from all participants. Eleven consecutive patients with Crohn disease (eight female patients, three men; mean age, 39.5 years; range, 16.4-66.6 years) undergoing elective small-bowel resection were recruited between July 2006 and December 2007. Harvey-Bradshaw index, C-reactive protein (CRP) level, and disease chronicity were recorded. Preoperatively, dynamic contrast-enhanced MR imaging was performed through the section of bowel destined for resection, and slope of enhancement, time to maximum enhancement, enhancement ratio, the volume transfer coefficient K(trans), and the extracellular volume fraction v(e) were calculated for the affected segment. Ex vivo surgical specimens were imaged to facilitate imaging-pathologic correlation. Histopathologic sampling of the specimen was performed through the imaged tissue, and microvascular density (MVD) was determined, together with acute and chronic inflammation scores. Correlations between clinical, MR imaging, and histopathologic data were made by using the Kendall rank correlation and linear regression. RESULTS Disease chronicity was positively correlated with enhancement ratio (correlation coefficient, 0.82; P = .002). Slope of enhancement demonstrated a significant negative correlation with MVD (correlation coefficient, -0.86; P < .001). There was a negative correlation between CRP level and slope of enhancement (correlation coefficient, -0.77; P = .006). Neither acute nor chronic inflammation score correlated with any other parameter. CONCLUSION Certain MR imaging-derived mural hemodynamic parameters correlate with disease chronicity and angiogenesis in Crohn disease, but not with histologic and clinical markers of inflammation. Data support the working hypothesis that microvessel permeability increases with disease chronicity and that tissue MVD is actually inversely related to mural blood flow.

Pediatric and Adolescent Lymphoma: Comparison of Whole-Body STIR Half-Fourier RARE MR Imaging with an Enhanced PET/CT Reference for Initial Staging

PURPOSE To compare the diagnostic performance of rapid whole-body anatomic magnetic resonance (MR) staging of pediatric and adolescent lymphoma to an enhanced positron emission tomographic (PET)/computed tomographic (CT) reference standard. MATERIALS AND METHODS Ethical permission was given by the University College London Hospital ethics committee, and informed written consent was obtained from all participants and/or parents or guardians. Thirty-one subjects (age range, 7.3-18.0 years; 18 male, 11 female) with histologically proved lymphoma were prospectively recruited. Pretreatment staging was performed with whole-body short inversion time inversion-recovery (STIR) half-Fourier rapid acquisition with relaxation enhancement (RARE) MR imaging, fluorine 18 fluorodeoxyglucose PET/CT, and contrast agent-enhanced chest CT. Twenty-six subjects had posttreatment PET/CT and compromised our final cohort. Eleven nodal and 11 extranodal sites per patient were assessed on MR imaging by two radiologists in consensus, with a nodal short-axis threshold of >1 cm and predefined extranodal positivity criteria. The same sites were independantly evaluated by two nuclear medicine physicians on PET/CT images. Disease positivity was defined as a maximum standardized uptake value >2.5 or nodal size >1 cm. An unblinded expert panel reevaluated the imaging findings, removing perceptual errors, and derived an enhanced PET/CT reference standard (taking into account chest CT and 3-month follow-up imaging) against which the reported and intrinsic performance of MR imaging was assessed by using the kappa statistic. RESULTS There was very good agreement between MR imaging and the enhanced PET/CT reference standard for nodal and extranodal staging (kappa = 0.96 and 0.86, respectively) which improved following elimination of perceptual errors (kappa = 0.97 and 0.91, respectively). The sensitivity and specificity of MR imaging (following removal of perceptual error) were 98% and 99%, respectively, for nodal disease and 91% and 99%, respectively, for extranodal disease. CONCLUSION Whole-body STIR half-Fourier RARE MR imaging of pediatric and adolescent lymphoma can accurately depict nodal and extranodal disease and may provide an alternative nonionizing imaging method for anatomic disease assessment at initial staging.

Xenon augmented hypothermia reduces early lactate/N-acetylaspartate and cell death in perinatal asphyxia

Additional treatments for therapeutic hypothermia are required to maximize neuroprotection for perinatal asphyxial encephalopathy. We assessed neuroprotective effects of combining inhaled xenon with therapeutic hypothermia after transient cerebral hypoxia–ischemia in a piglet model of perinatal asphyxia using magnetic resonance spectroscopy (MRS) biomarkers supported by immunohistochemistry.

Depth of delayed cooling alters neuroprotection pattern after hypoxia-ischemia

Hypothermia after perinatal hypoxia‐ischemia (HI) is neuroprotective; the precise brain temperature that provides optimal protection is unknown. To assess the pattern of brain injury with 3 different rectal temperatures, we randomized 42 newborn piglets: (Group i) sham‐normothermia (38.5–39°C); (Group ii) sham‐33°C; (Group iii) HI‐normothermia; (Group iv) HI‐35°C; and (Group v) HI‐33°C. Groups iii through v were subjected to transient HI insult. Groups ii, iv, and v were cooled to their target rectal temperatures between 2 and 26 hours after resuscitation. Experiments were terminated at 48 hours. Compared with normothermia, hypothermia at 35°C led to 25 and 39% increases in neuronal viability in cortical gray matter (GM) and deep GM, respectively (both p < 0.05); hypothermia at 33°C resulted in a 55% increase in neuronal viability in cortical GM (p < 0.01) but no significant increase in neuronal viability in deep GM. Comparing hypothermia at 35 and 33°C, 35°C resulted in more viable neurons in deep GM, whereas 33°C resulted in more viable neurons in cortical GM (both p < 0.05). These results suggest that optimal neuroprotection by delayed hypothermia may occur at different temperatures in the cortical and deep GM. To obtain maximum benefit, you may need to design patient‐specific hypothermia protocols by combining systemic and selective cooling. Ann Neurol 2005;58:75–87

High-resolution fast spin echo imaging of the human brain at 4.7 T: Implementation and sequence characteristics

In this work, a number of important issues associated with fast spin echo (FSE) imaging of the human brain at 4.7 T are addressed. It is shown that FSE enables the acquisition of images with high resolution and good tissue contrast throughout the brain at high field strength. By employing an echo spacing (ES) of 22 ms, one can use large flip angle refocusing pulses (162°) and a low acquisition bandwidth (50 kHz) to maximize the signal‐to‐noise ratio (SNR). A new method of phase encode (PE) ordering (called “feathering”) designed to reduce image artifacts is described, and the contributions of RF (B1) inhomogeneity, different echo coherence pathways, and magnetization transfer (MT) to FSE signal intensity and contrast are investigated. B1 inhomogeneity is measured and its effect is shown to be relatively minor for high‐field FSE, due to the self‐compensating characteristics of the sequence. Thirty‐four slice data sets (slice thickness = 2 mm; in‐plane resolution = 0.469 mm; acquisition time = 11 min 20 s) from normal volunteers are presented, which allow visualization of brain anatomy in fine detail. This study demonstrates that high‐field FSE produces images of the human brain with high spatial resolution, SNR, and tissue contrast, within currently prescribed power deposition guidelines. Magn Reson Med 51:1254–1264, 2004.

Delayed whole-body cooling to 33 or 35 degrees C and the development of impaired energy generation consequential to transient cerebral hypoxia-ischemia in the newborn piglet.

OBJECTIVES. Fundamental questions remain about the precise temperature providing optimal neuroprotection after perinatal hypoxia-ischemia (HI). Furthermore, if hypothermia delays the onset of the neurotoxic cascade and the secondary impairment in cerebral energy generation, the “latent phase” may be prolonged, thus extending the period when additional treatments may be effective. The aims of this study were to investigate the effects of delayed systemic cooling at either 33°C or 35°C on the following: (1) latent-phase duration, and (2) cerebral metabolism during secondary energy failure itself, in the 48-hour period after transient HI. METHODS. Piglets were randomly assigned to the following: (1) HI-normothermic (HI-n) rectal temperature (Trectal; n = 12), (2) HI-Trectal 35°C (HI-35; n = 7), and (3) HI-Trectal 33°C (HI-33; n = 10). Groups were cooled to the target Trectal between 2 and 26 hours after HI. Serial magnetic resonance spectroscopy was performed over 48 hours. The effect of cooling on secondary energy failure severity (indexed by the nucleotide triphosphate/exchangeable phosphate pool [NTP/EPP] and phosphocreatine/inorganic phosphate [PCr/Pi] ratios) was assessed. RESULTS. Compared with HI-n, HI-35 and HI-33 had a longer NTP/EPP latent phase and during the entire study duration had higher mean NTP/EPP and PCr/Pi. The latent phase (both PCr/Pi and NTP/EPP) and the whole-brain cerebral energetics were similar for HI-35 and HI-33. During the hypothermic period, compared with HI-n, PCr/Pi was preserved in the cooled groups, but this advantage was not maintained after rewarming. Compared with HI-n, HI-35 and HI-33 had higher NTP/EPP after rewarming. CONCLUSIONS. Whole-body hypothermia for 24 hours at either 35 or 33°C, commenced 2 hours after resuscitation, prolonged the NTP/EPP latent phase and reduced the overall secondary falls in mean PCr/Pi and NTP/EPP during 48 hours after HI. Reducing the temperature from 35 to 33°C neither increased mean PCr/Pi and NTP/EPP nor further lengthened the latent phase.

T2 at MR Imaging Is an Objective Quantitative Measure of Cerebral White Matter Signal Intensity Abnormality in Preterm Infants at Term-equivalent Age

PURPOSE To compare quantitative T2 relaxometry of cerebral white matter (WM) with qualitative assessment of conventional T2-weighted magnetic resonance (MR) images, to assess the relationship between cerebral WM T2 and region-specific apparent diffusion coefficient (ADC), and to examine WM T2 regional variation in preterm infants at term. MATERIALS AND METHODS The local ethical committee granted ethical permission for this study; informed parental consent was obtained for each infant. Sixty-two preterm infants born at less than 32 weeks gestation and nine control infants were examined at 1.5 T; T2-weighted fast spin-echo MR images, T2 relaxometry data, and diffusion-weighted MR images were acquired. Conventional T2-weighted MR images were assessed by a pediatric neuroradiologist for diffuse excessive high signal intensity (DEHSI) in WM. Regions of interest were positioned in frontal WM, central WM, and posterior WM at the level of the centrum semiovale. RESULTS In preterm infants at term, T2 was longer in all WM regions than in control infants; in infants with DEHSI, T2 was longer than in infants without DEHSI and control infants, with posterior WM T2 being longer than central or frontal WM T2. In control infants, T2 was similar in all WM regions. Frontal and posterior WM ADCs were higher in preterm infants at term than in control infants. CONCLUSION Cerebral WM T2 is an objective quantitative measurement that can easily and rapidly be obtained during clinical MR imaging in preterm infants at term.