99mTc-HMPAO-leukocyte scintigraphy for diagnosis and therapy monitoring of skull base osteomyelitis.

OBJECTIVE: Skull base osteomyelitis (SBO) is a rare but life-threatening disease observed in elderly diabetic patients, with high risk of recurrence and difficult therapeutic management. The diagnosis is ascertained from a set of clinical, biological, and imaging findings. CT and MRI allow initial diagnosis, but are not accurate to affirm healing at the end of therapy. 99mTc-HMPAO-Leucocyte Scintigraphy (LS) is highly sensitive and specific for the detection of infection. The aim of this study was to evaluate LS i) for initial diagnosis, and ii) to confirm healing at the end of antibiotherapy in SBO. STUDY DESIGN: We retrospectively reviewed from November 2011 to September 2015 all patients with confirmed SBO who underwent LS twice, at diagnosis and at the end of antibiotic therapy in our nuclear medicine department (n = 27). METHODS: Clinical, biological, CT, LS, and follow-up data were recorded in all patients. LS images (planar and tomographic performed 4 hours and 24 hours after intravenous injection of autologous Tc-99m-HMPAO-leucocytes) were visually assessed and quantified. RESULTS: At initial diagnosis, 25 of 27 patients had a positive LS. At the end of antibiotic therapy (3 ± 1 months duration), 26 of 27 patients had a negative LS. During subsequent follow-up (= or >6 months), the disease recurred in four patients including three with a negative postantibiotherapy LS scan. CONCLUSION: In this retrospective study, LS was powerful for initial diagnostic of SBO and for healing assessment at the end of antibiotic therapy. We conclude it is a useful technique for therapeutic monitoring of SBO. LEVEL OF EVIDENCE: 4.

Diffusion tensor imaging tractography parameters of limbic system bundles in temporal lobe epilepsy patients.

PURPOSE: To investigate changes in diffusion tensor imaging (DTI) measures in limbic system white matter of patients with temporal lobe epilepsy (TLE) using diffusion tensor tractography. MATERIALS AND METHODS: DTI metrics including fractional anisotropy (FA), λ1, λ2, λ3, and trace (Tr) coefficients were obtained from tractography for bilateral fornix, superior and inferior cingulum fibers in 18 patients and 10 healthy controls. Hippocampal signal-to-noise ratio (SNR) quantitative analysis was performed in order to confirm the magnetic resonance imaging (MRI) hippocampal lesion presence or absence in TLE patients. RESULTS: Nine patients presented unilateral hippocampal sclerosis (TLE+HS) and nine patients had no signal abnormalities on conventional MRI (TLE-HS). On the ipsilateral seizure side, all three investigated tracts showed significant DTI indices abnormalities in both patient groups when compared with controls, most marked on the inferior cingulum. Contralateral to the seizure side, the three tracts presented significant DTI parameters in only the TLE+HS group when compared with controls. CONCLUSION: The DTI abnormalities found in the TLE-HS group may suggest that in the inferior cingulum the structural integrity is more affected than in the fornix or superior cingulum white matter bundles. The eigenvalues taken separately add complementary information to the FA and Tr metrics and may be useful indices in better understanding the architectural reorganization of limbic system tracts in TLE patients without HS.

Gefitinib-phenytoin interaction is not correlated with the C-erythromycin breath test in healthy male volunteers.

AIMS: We aimed to describe the pharmacokinetic interaction between phenytoin, a potent CYP3A4 and P-glycoprotein (P-gp) (ABCB1) inducer, and gefitinib, a CYP3A4, CYP2D6 and P-gp substrate. METHODS: An open-label, randomized, two-phase crossover study was conducted. Eighteen healthy male volunteers (nine homozygous CC and nine homozygous TT as determined by their ABCB1 C3435T polymorphism in exon 26) received a single oral dose of 250 mg gefitinib alone or after 5 days treatment with phenytoin (5 mg kg(-1) daily). Gefitinib plasma concentrations were determined by high-performance liquid chromatography. Hepatic CYP3A4 activity was evaluated by the (14)C-erythromycin breath test (ERMBT) and the ABCB1 and CYP2D6 genetic polymorphisms were determined by the TaqMan allelic discrimination assay and long polymerase chain reaction, respectively. RESULTS: Following treatment with phenytoin, mean gefitinib C(max) and AUC(0-infinity) decreased by 26 +/- 44% [95% confidence interval (CI) for the difference 5-48%, P= 0.005] and 47 +/- 26% (95% CI for the difference 34-60%, P= 0.001), respectively, and apparent oral clearance increased by 126 +/- 93% (95% CI for the difference 80-172%, P= 0.004). Concomitantly, phenytoin increased the mean ERMBT by 91 +/- 44% (95% CI 75-105%, P < 0.001) from baseline, but the extent of liver CYP3A4 induction was not correlated to the extent of interaction. Furthermore, this interaction was independent of ABCB1 genetic polymorphism. The CYP2D6 genotype was slightly but significantly related to gefitinib clearance (P= 0.04) during the control phase. CONCLUSIONS: The significant interaction between gefitinib and phenytoin was not correlated with the erythromycin breath test and was independent of ABCB1 polymorphism, but may involve presystemic CYP3A-mediated intestinal first-pass.

Age-related cerebral white matter changes and pulse-wave encephalopathy: observations with three-dimensional MRI.

Our purpose was to investigate leukoaraïosis (LA) using three-dimensional MR imaging combined with advanced image-processing technology to attempt to group signal abnormalities according to their etiology. Coronal T2-weighted fast fluid-attenuated inversion-recovery (FLAIR) sequences and three-dimensional T1-weighted fast spoiled gradient recalled echo sequences were used to examine cerebral white matter changes in 75 elderly people with memory complaint but no dementia. They were otherwise healthy, community-dwelling subjects. Three subtypes of LA were defined on the basis of their shape, geography and extent: the so-called subependymal/subpial LA, perivascular LA and "bands" along long white matter tracts. Subependymal changes were directly contiguous with ventricular spaces. They showed features of "water hammer" lesions with ventricular systematisation and a more frequent location around the frontal horns than around the bodies (P=.0008). The use of cerebrospinal fluid (CSF) contiguity criterion allowed a classification of splenial changes in the subpial group. Conversely, posterior periventricular lesions in the centrum ovale as well as irregular and extensive periventricular lesions were not directly contiguous with CSF spaces. The so-called perivascular changes showed features of small-vessel-associated disease; they surrounded linear CSF-like signals that followed the direction of perforating vessels. Distribution of these perivascular changes appeared heterogeneous (P ranging from .04 to 5.10(-16)). These findings suggest that subependymal/subpial LA and subcortical LA may be separate manifestations of a single underlying pulse-wave encephalopathy.

Intracranial fluid dynamics in normal and hydrocephalic states: systems analysis with phase-contrast magnetic resonance imaging.

OBJECTIVE: To present a novel magnetic resonance (MR) method of analysis of cerebrospinal fluid (CSF) flow dynamics. METHODS: Fifty-one subjects were explored with phase-contrast cine MR imaging. There were 36 volunteers, 9 patients with normal pressure hydrocephalus (NPH), and 6 patients with asymptomatic ventricular dilation (VD). The transfer function XFRA/CSF from the arterial pulse waves (APWs) and the CSF pulse waves (CSFPWs) and the transfer function XFRCSF/SS from the CSF pulse waves (CSFPWs) and the sagittal sinus pulse waves (SSPWs) were studied separately. RESULTS: There was a significant difference in the amplitude spectrum of the XFRA/CSF of patients with VD and volunteers (P < 0.05) and in that of patients with NPH and volunteers (P = 0.005). The amplitude of the fundamental frequency was higher in the NPH group than in the VD group (P = 0.02). In patients with NPH, the amplitude spectrum of XFRCSF/SS showed an attenuation of the pulse wave components that significantly differed from the observed amplification in healthy subjects (P = 0.009) and patients with VD (P = 0.012). CONCLUSION: This systems analysis method could help to detect increased venous compliance in VD and decreased venous compliance in NPH.

Relationship between cerebrospinal fluid and blood dynamics in healthy volunteers and patients with communicating hydrocephalus.

RATIONALE AND OBJECTIVES: Using magnetic resonance imaging (MRI), we investigated cerebral blood and cerebrospinal fluid (CSF) flows in patients with communicating hydrocephalus (CH) and in healthy volunteers to determine the contribution of CSF flow to brain pressure regulation in CH patients. METHODS: Cine phase-contrast MRI data from 16 healthy volunteers and 12 patients with CH characterized by hyperdynamic aqueductal CSF flow were analyzed using in-house image-processing software that automatically measured flow curves. Amplitude and temporal CSF and blood flow parameters were compared in the 2 groups. RESULTS: Jugular peak flow occurred significantly earlier (P < 0.01) in the CH patients than in the healthy volunteers. Cervical CSF oscillations were not significantly different between the 2 groups. CONCLUSION: Venous vessel compression and/or changes in intracranial subarachnoid CSF flow produce an increase in ventricular CSF flush that compensates for vascular brain expansion in patients with CH.

Leukoaraiosis and mobility decline: a high resolution magnetic resonance imaging study in older people with mild cognitive impairment.

Patterns of leukoaraiosis were analyzed on both T2-weighted fast fluid-attenuated inversion-recovery and 3D T1-weighted sequences in 23 community-dwelling older subjects with mild cognitive impairment. Mobility assessment had allowed their classification into higher and lower mobility groups (P<0.0001). Lower mobility appeared correlated with frontal subependymal lesions (P=0.0005). The absence of marked ventriculomegaly, any thick caps, deep white matter lesions curved along the ventricles bodies, large deep white matter lesions, deep grey matter leukoaraiosis was an hallmark of the higher mobility group (P<0.0001). High resolution MRI demonstrated regular patterns of the subependymal lesions and detected perivascular distribution in other forms of leukoaraiosis. It suggests that the underlying mechanism of mobility decline in the elderly may be impairment of cerebrospinal fluid dynamics with cerebral small vessel disease.

Differential MRI diagnosis between brain abscesses and necrotic or cystic brain tumors using the apparent diffusion coefficient and normalized diffusion-weighted images.

Magnetic Resonance Diffusion-Weighted Imaging (DWI) has been reported to be helpful for the differential diagnosis between abscesses and cystic/necrotic brain tumors. However the number of patients is still limited, and the sensitivity and specificity of the method remain to be confirmed. The primary purpose of this study was to investigate a larger sample of patients, all investigated under the same experimental conditions, in order to obtain statistically significant data. Moreover, there is no consensus about the appropriate values of b required to use to make an accurate diagnosis from DWI. The secondary purpose of this study was to determine the discriminating threshold b values for raw diffusion-weighted images and for normalized diffusion-weighted images. On the basis of 14 abscesses, 10 high-grade gliomas and 2 metastases, we show that the calculation of accurate Apparent Diffusion Coefficient (ADC) values gives a specificity rate of 100%. Without ADC calculation, we show that image normalization is required to make an accurate differential diagnosis, and we highlight the ability of DWI to discriminate between brain abscesses and cystic/necrotic brain tumors using normalized signal intensity at lower b values (503 s/mm(2)) than usual.

Comparative value of ECG-gated blood pool SPET and ECG-gated myocardial perfusion SPET in the assessment of global systolic left ventricular function.

Both electrocardiographically (ECG) gated blood pool SPET (GBPS) and ECG-gated myocardial perfusion SPET (GSPET) are currently used for the measurement of global systolic left ventricular (LV) function. In this study, we aimed to compare the value of GSPET and GBPS for this purpose. The population included 65 patients who underwent rest thallium-201 GSPET imaging at 15 min after (201)Tl injection followed by planar (planar(RNA)) and GBPS equilibrium radionuclide angiography immediately after 4-h redistribution myocardial perfusion SPET imaging. Thirty-five patients also underwent LV conventional contrast angiography (X-rays). LV ejection fraction (EF) and LV volume [end-diastolic (EDV) and end-systolic (ESV) volumes] were calculated with GBPS and GSPET and compared with the gold standard methods (planar(RNA) LVEF and X-ray based calculation of LV volume). For both LVEF and LV volume, the inter-observer variability was lower with GBPS than with GSPET. GBPS LVEF was higher than planar(RNA) (P<0.01) and GSPET LVEF (P<0.01). Planar(RNA) LVEF showed a slightly better correlation with GBPS LVEF than with GSPET LVEF: r=0.87 and r=0.83 respectively. GSPET LV volume was lower than that obtained using X-rays and GBPS (P<0.01 for both). LV volume calculated using X-rays showed a slightly better correlation with GBPS LV volume than with GSPET LV volume: r=0.88 and r=0.83 respectively. On stepwise regression analysis, the accuracy of GSPET for the measurement of LVEF and LV volume was correlated with a number of factors, including planar(RNA) LVEF, signal to noise ratio, LV volume calculated using X-rays, summed rest score and acquisition scan distance (i.e. the radius of rotation). The accuracy of GBPS for the measurement of LVEF and LV volume was correlated only with the signal level, the signal to noise ratio and the acquisition scan distance. Both GSPET and GBPS provide reliable estimation of global systolic LV function. The better reliability of GBPS and in particular its lower sensitivity to different variables as compared with GSPET favours its use when precise assessment of global systolic LV function is clinically indicated.