Endolymphatic hydrops asymmetry distinguishes patients with Meniere's disease from normal controls with high sensitivity and specificity.

Background: Many endolymphatic hydrops (EH) MRI studies in the literature do not include a normal control group. Consequently, it remains unclear which outcome measure in EH MRI can most effectively distinguish between MD patients and normal controls. Methods: Gadolinium-enhanced EH imaging was performed to quantitatively evaluate the extents of hydrops in MD patients and age-/sex-matched normal controls. Four hours after intravenous injection of contrast agent, MRI was performed using a 3-T MR platform fitted with a 32-channel phased-array coil receptor. MR images (10-15 slices) covering an inner ear were 3D-stacked. Analyses of all images that included the vestibule or the cochlea yielded the volumes (in µL) of the endolymphatic and perilymphatic spaces. Results: For the vestibule, they were significantly greater EH% in ipsilateral (52.4 ± 12.5) than in contralateral MD ears (40.4 ± 8.5, p = 0.001) and in ipsilateral MD ears than in control ears (42.4 ± 13.7, p = 0.025). For the cochlea, the values were slightly higher EH% in ipsilateral MD ears (49.7 ± 10.4, p = 0.061) but did not significantly differ from contralateral (41.3 ± 12.6) or control ears (39.6 ± 18.9, p = 0.858). In the MD group, the EH asymmetries were 12.0 ± 10.2% (vestibule) and 8.4 ± 8.6% (cochlea), significantly larger than those of controls. Conclusion: Compared to conventional semiquantitative grading or quantitative EH% analysis, EH asymmetry may better distinguish MD patients from normal controls. Quantitative hydrops volumetric analysis yields clinically relevant information on inner ear function.

Synaptic Remodeling of the Auditory Cortex Following Bilateral Blindness: Evidence of Cross-modal Plasticity.

We aimed to evaluate structural dynamic changes of neurons in the auditory cortex after visual deprivation. We longitudinally tracked dendritic spines for 3 weeks after visual deprivation in vivo using a two-photon microscope. GFP-labeled dendritic spines in the auditory cortex were serially followed after bilateral enucleation. The turnover rate, density, and size of the spines in the dendrites were evaluated 1, 2, and 3 weeks after visual deprivation. The turnover rate of the dendritic spines in the auditory cortex increased at 1 week (20.1±7.3%) after bilateral enucleation compared to baseline (12.5±7.9%); the increase persisted for up to 3 weeks (20.9±11.0%). The spine loss rate was slightly higher than the spine gain rate. The average spine density (number of spines per 1 µm of dendrite) was significantly lower at 2 weeks (2W; 0.22±0.06 1/µm) and 3 W (0.22±0.08 1/µm) post-nucleation compared to baseline (0.026±0.09 1/µm). We evaluated the change of synaptic strength in the stable spines at each time point. The normalized spine size in the auditory cortex was significantly increased after bilateral blindness at 1 W postoperatively (1.36±0.92), 2 W postoperatively (1.40±1.18), and 3 W postoperatively (1.36±0.88) compared to baseline. Sensory deprivation resulted in remodeling of the neural circuitry in the spared cortex, via cross-modal plasticity in the direction of partial breakdown of synapses, and enhanced strength of the remaining synapses.

Cross-Modal Cortical Activity in the Brain Can Predict Cochlear Implantation Outcome in Adults: A Machine Learning Study.

OBJECTIVES: Prediction of cochlear implantation (CI) outcome is often difficult because outcomes vary among patients. Though the brain plasticity across modalities during deafness is associated with individual CI outcomes, longitudinal observations in multiple patients are scarce. Therefore, we sought a prediction system based on cross-modal plasticity in a longitudinal study with multiple patients. METHODS: Classification of CI outcomes between excellent or poor was tested based on the features of brain cross-modal plasticity, measured using event-related responses and their corresponding electromagnetic sources. A machine learning estimation model was applied to 13 datasets from 3 patients based on linear supervised training. Classification efficiency was evaluated comparing prediction accuracy, sensitivity/specificity, total mis-classification cost, and training time among feature set conditions. RESULTS: Combined feature sets with the sensor and source levels dramatically improved classification accuracy between excellent and poor outcomes. Specifically, the tactile feature set best explained CI outcome (accuracy, 98.83 ± 2.57%; sensitivity, 98.00 ± 0.01%; specificity, 98.15 ± 4.26%; total misclassification cost, 0.17 ± 0.38; training time, 0.51 ± 0.09 sec), followed by the visual feature (accuracy, 93.50 ± 4.89%; sensitivity, 89.17 ± 8.16%; specificity, 98.00 ± 0.01%; total misclassification cost, 0.65 ± 0.49; training time, 0.38 ± 0.50 sec). CONCLUSION: Individual tactile and visual processing in the brain best classified the current status when classified by combined sensor-source level features. Our results suggest that cross-modal brain plasticity due to deafness may provide a basis for classifying the status. We expect this novel method to contribute to the evaluation and prediction of CI outcomes.

Three-Dimensional Volumetric Measurement of Endolymphatic Hydrops in Meniere's Disease.

Objective: We used volumetric three-dimensional (3D) analysis to quantitatively evaluate the extent of endolymphatic hydrops (EH) in the entire inner ear. We tested for correlations between the planimetric and volumetric measurements, to identify their advantages and disadvantages. Methods: HYDROPS2-Mi2 EH images were acquired for 32 ears (16 patients): 16 ipsilateral ears of MD patients (MD-ears) and 16 contralateral ears. Three-T MR unit with a 32-channel phased-array coil/the contrast agent to fill the perilymphatic space and the HYDROPS2-Mi2 sequence. We calculated the EH% [(endolymph)/(endolymph+perilymph)] ratio and analyzed the entire inner ear in terms of the volumetric EH% value, but only single cochlear and vestibular slices were subjected to planimetric EH% evaluation. The EH% values were compared between MD ears and non-MD ears, to evaluate the diagnostic accuracy of the two methods. Results: The volumetric EH% was significantly higher for MD vestibules (50.76 ± 13.78%) than non-MD vestibules (39.50 ± 8.99%). The planimetric EH% was also significantly higher for MD vestibules (61.98 ± 20.65%) than non-MD vestibules (37.22 ± 12.95%). The vestibular and cochlear volumetric EH% values correlated significantly with the planimetric EH% values of the MD ear. Conclusion: Volumetric and planimetric EH measurements facilitate diagnosis of MD ears compared to non-MD ears. Both methods seem to be reliable and consistent; the measurements were significantly correlated in this study. However, the planimetric EH% overestimates the extent of vestibular hydrops by 26.26%. Also, planimetric data may not correlate with volumetric data for non-MD cochleae with normal EH% values.

Effect and Biocompatibility of a Cross-Linked Hyaluronic Acid and Polylactide-co-glycolide Microcapsule Vehicle in Intratympanic Drug Delivery for Treating Acute Acoustic Trauma.

The treatment of acute hearing loss is clinically challenging due to the low efficacy of drug delivery into the inner ear. Local intratympanic administration of dexamethasone (D) and insulin-like growth factor 1 (IGF1) has been proposed for treatment, but they do not persist in the middle ear because they are typically delivered in fluid form. We developed a dual-vehicle drug delivery system consisting of cross-linked hyaluronic acid and polylactide-co-glycolide microcapsules. The effect and biocompatibility of the dual vehicle in delivering D and IGF1 were evaluated using an animal model of acute acoustic trauma. The dual vehicle persisted 10.9 times longer (8.7 days) in the middle ear compared with the control (standard-of-care vehicle, 0.8 days). The dual vehicle was able to sustain drug release over up to 1 to 2 months when indocyanine green was loaded as the drug. One-third of the animals experienced an inflammatory adverse reaction. However, it was transient with no sequelae, which was validated by micro CT findings, endoscopic examination, and histological assessment. Hearing restoration after acoustic trauma was satisfactory in both groups, which was further supported by comparable numbers of viable hair cells. Overall, the use of a dual vehicle for intratympanic D and IGF1 delivery may maximize the effect of drug delivery to the target organ because the residence time of the vehicle is prolonged.

Effect of age on the gap-prepulse inhibition of the cortical N1-P2 complex in humans as a step towards an objective measure of tinnitus.

The gap-prepulse inhibition of the acoustic startle reflex has been widely used as a behavioral method for tinnitus screening in animal studies. The cortical-evoked potential gap-induced inhibition has also been investigated in animals as well as in human subjects. The present study aimed to investigate the effect of age on the cortical N1-P2 complex in the gap-prepulse inhibition paradigm. Fifty-seven subjects, aged 20 to 68 years, without continuous tinnitus, were tested with two effective gap conditions (embedded gap of 50- or 20-ms duration). Retest sessions were performed within one month. A significant gap-induced inhibition of the N1-P2 complex was found in both gap durations. Age differently affected the inhibition, depending on gap duration. With a 50-ms gap, the inhibition decreased significantly with the increase in age. This age-inhibition relationship was not found when using a 20-ms gap. The results were reproducible in the retest session. Our findings suggest that the interaction between age and gap duration should be considered when applying the gap-induced inhibition of the cortical-evoked potential as an objective measure of tinnitus in human subjects. Further studies with tinnitus patients are warranted to identify gap duration that would minimize the effects of age and maximize the difference in the inhibition between those with and without tinnitus.

Dual-site rTMS is More Effective than Single-site rTMS in Tinnitus Patients: A Blinded Randomized Controlled Trial.

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as an alternative option for treating tinnitus. rTMS is a noninvasive method in which repetitive magnetic stimulation is applied to the cortex; it is considered a therapeutic strategy that modulates the loudness of tinnitus. In this study, we performed a double-blind randomized clinical trial to compare the outcome of tinnitus treatment among (1) dual-site (auditory + prefrontal) rTMS stimulation, (2) auditory cortex only rTMS stimulation (AC), and (3) sham stimulation. The left primary auditory cortex and left dorsolateral prefrontal cortex (DLPFC) were targeted independently of handedness or tinnitus laterality. Dual-site and auditory only groups were treated with a total of 12,000 pulses, 2000 pulses over the AC and 1000 pulses over the DLPFC (group 1), 3000 pulses over the AC only (group 2), and daily for 4 consecutive days. Dual-site group exhibited a significantly better ΔTinnitus Handicap Inventory (ΔTHI) score at 4, 8 weeks and 12 weeks after rTMS treatments compared with pre-treatment. However, there was no effect in the auditory only group. Also, there was no effect in sham group when THI scores were compared with that of the pre-treatment. These results are in line with the former studies that reported a better treatment effect by multiple site rTMS.

Biocompatibility and Therapeutic Effect of 3 Intra-Tympanic Drug Delivery Vehicles in Acute Acoustic Trauma.

INTRODUCTION: The aim of this study was to assess the biocompatibility of several intra-tympanic (IT) drug delivery vehicles and to compare hearing outcomes. MATERIALS AND METHODS: After acute acoustic trauma, rats were treated with IT 10 mg/mL dexamethasone phosphate (D) and divided into the following groups for drug delivery: saline + D (n = 15), hyaluronic acid (HA) + D (n = 17), and methoxy polyethylene glycol-b-polycaprolactone block copolymer (MP) + D (n = 24). RESULTS: No inflammation was found in the saline + D or HA + D groups. The duration of vehicle/drug persistence in the bulla was significantly longer for the MP + D (47.5 days) and HA + D groups (1.8 days) than for the saline + D group (<1 day). The tympanic membrane was significantly thicker in the MP + D group than in the saline + D and HA + D groups. The proportion of ears with good hearing outcome was significantly higher (63.6%) in the HA + D group than in the MP + D group. The number of hair cells in the hearing loss (HL) control group was significantly lower than in the MP + D group. DISCUSSION/CONCLUSION: HA shows great potential as a biocompatible vehicle for D delivery via the IT route, without an inflammatory reaction and with better hearing outcomes. Considering inflammation and hearing, MP may not be a good candidate for IT drug delivery.

Treatment Outcome of Auditory and Frontal Dual-Site rTMS in Tinnitus Patients and Changes in Magnetoencephalographic Functional Connectivity after rTMS: Double-Blind Randomized Controlled Trial.

BACKGROUND: Recently, the role of neural modulation in nonauditory cortices via repetitive transcranial magnetic stimulation (rTMS) for tinnitus control has been emphasized. It is now more compelling to consider these nonauditory cortices and the whole "tinnitus network" as targets for tinnitus treatment to achieve a better outcome. OBJECTIVE: We aimed to investigate the effects of active dual-site rTMS treatment in tinnitus reduction using a double-blind randomized controlled trial. METHOD: In study 1, the dual-site rTMS treatment group (n = 17) was treated daily for 4 consecutive days. The sham group (n = 13) also visited the clinic for 4 days; they received sham treatment for the same duration as the dual-site rTMS treatment group. In study 2, the rTMS treatment protocol was exactly the same as in study 1. Magnetoencephalography recordings were performed before and 1 week after the last rTMS treatment. The outcome measure was the Tinnitus Handicap Inventory (THI) score and the visual analog scale score. The effects of treatment were assessed 1, 2, 4, and 8 weeks after rTMS treatment in study 1. Then the mean band power and network changes were compared between pre- and post-treatment values after rTMS in study 2. RESULT: Patients in the dual-site rTMS treatment group exhibited significantly improved THI scores at 2, 4, and 8 weeks after rTMS treatment compared with the pretreatment scores. However, the sham group did not show any significant reduction in THI scores. When the mean band power changes were compared between pre- and post-treatment assessments, an increased oscillation power was observed in the alpha band after rTMS. CONCLUSION: A beneficial effect of rTMS on tinnitus suppression was found in the dual-site active rTMS group, but not in the sham rTMS group.

Phantom Perception of Sound and the Abnormal Cortical Inhibition System: An Electroencephalography (EEG) Study.

OBJECTIVES: Despite no observable external sound present, a perceived feeling of a recurrent unpleasant sound is a main complaint in the patients with chronic tinnitus. This phantom perception of sound is considered as the auditory equivalent of phantom limb pain, and altered excitability may be involved in its underlying pathology. Tinnitus-related hyper-excitation is suppressed by inhibitory repetitive transcranial magnetic stimulation (rTMS). However, the neural mechanism underlying the treatment is not fully understood, and quantifying the suppression induced by rTMS has yet to be considered. METHODS: We evaluated the effect of rTMS on the cortical inhibition status following single-site stimulation over the auditory temporal cortex (T group) or dual-site stimulation over the auditory temporal and the frontal regions (TF group). These effects were also compared with outcomes following sham stimulation (S group). Subjective response was recorded using tinnitus-related handicap index (THI), and changes in the cortical inhibition status were assessed using an auditory paired-pulse suppression index (PPSI). RESULTS: TF group showed the greatest benefit from the treatment evidenced in the reduced PPSI and THI scores. T and S groups did not benefit much. TF group overlapped mostly with the responder group, indicating improvement in both subjective THI and objective PPSI measurements. CONCLUSION: Our results suggest that rTMS is a beneficial therapeutic treatment for chronic tinnitus patients and the dual-site treatment was the most effective in terms of both tinnitus complaint and quantitative indices. Thus, subjective reports and electrophysiological signatures may be complementary for the diagnosis/prognosis of tinnitus.

Comparison of treatment outcomes between 10 and 20 EEG electrode location system-guided and neuronavigation-guided repetitive transcranial magnetic stimulation in chronic tinnitus patients and target localization in the Asian brain.

OBJECTIVE: rTMS is a non-invasive method that applies a brief magnetic pulse to the cortex and is regarded as a possible therapeutic method for tinnitus control. However, it remains unclear whether the rTMS treatment effect would be the same in tinnitus patients receiving the 10-20 EEG-based target localization as in those receiving imaging-based neuronavigation target localization. METHODS: We compared the treatment outcome of the 10-20 EEG-guided rTMS (Group 1) with that of the neuronavigation-guided rTMS (Group 2). Using the individual subject's MRI data and neuronavigation system, the coordinates of the AC relative to the 10-20 EEG system were identified in Asian and compared with those of Caucasian. RESULTS: There was significant improvement in the THI and VAS scores in Group 1 and 2. However, there was no significant difference between the two groups. The location of the AC in Asians was significantly different to that in Caucasians. CONCLUSION: The 10-20 EEG coordinates of the AC in Asians were significantly different to those in Caucasians. To accurately aim for the AC in Asians, it is recommended that the rTMS be located 1.8 cm superior to the T3 and 0.6 cm posterior to the T3-Cz line. However, because the spatial resolution of the TMS is rather low, this difference probably was not reflected in the treatment outcome.

Comparison of Treatment Outcomes Following Either Prefrontal Cortical-only or Dual-site Repetitive Transcranial Magnetic Stimulation in Chronic Tinnitus Patients: A Double-blind Randomized Study.

OBJECTIVES: We evaluated treatment outcomes following single-site repetitive transcranial magnetic stimulation (rTMS) in the dorsolateral prefrontal cortex (DLPFC) and dual-site rTMS in the auditory cortex (AC) and DLPFC (AC + FC). STUDY DESIGN AND PATIENTS: This prospective randomized double-blind trial initially included 19 patients with chronic tinnitus and 17 of these patients received rTMS on the left AC and left DLPFC or only the left DLPFC. The subjects were randomly allocated to either the dual-site rTMS (AC + FC) protocol (Group 1, n = 9) or the singlesite rTMS (DLPFC) protocol (Group 2, n = 8). Group 1 received daily treatments with 2,000 pulses applied to the AC and 1,000 pulses applied to the DLPFC for 4 days (total of 12,000 pulses) and Group 2 received daily treatments with 3,000 pulses applied the DLPFC for 4 days (total of 12,000 pulses). MAIN OUTCOME MEASURES: The severity of tinnitus was assessed before rTMS treatment using the Tinnitus Handicap Inventory (THI) and the self-rated Visual Analog Scale. These measures were used to determine the awareness, loudness, annoyance, and effects of tinnitus on daily life at 1, 2, 4, and 12 weeks after treatment. RESULTS: The improvement in THI score was significantly better in Group 1 than in Group 2, even after controlling for the between-group differences in pretreatment THI score. In terms of psychological factors, Group 1 exhibited significant improvements in scores on the State-Trait Anxiety Inventory (STAI) for both state anxiety (STAI-X1) and trait anxiety (STAI-X2) at 12 weeks posttreatment and scores on the Pittsburgh Sleep Quality Index at 4 weeks posttreatment. Group 2 showed an improvement in only the STAI-X2 score at 12 weeks posttreatment. CONCLUSIONS: The rTMS protocol effectively suppressed tinnitus in the dual-site rTMS (AC+FC) group but not in the single-site rTMS (DLPFC) group. Although recent evidence has shown that non-auditory cortices in the tinnitus network play an important role in the generation of tinnitus, our findings indicate that rTMS on non-auditory cortical sites alone may not be sufficient for treatment. Thus, dual-site rTMS in the AC and DLPFC may be preferable for controlling this condition.

Hepatic FDG uptake is associated with future cardiovascular events in asymptomatic individuals with non-alcoholic fatty liver disease.

BACKGROUND: Hepatic F-18 fluoro-2-deoxyglucose (FDG) uptake is associated with non-alcoholic fatty liver disease (NAFLD) which is an independent risk factor for cardiovascular disease. However, the value of hepatic FDG uptake for predicting future cardiovascular events has not been explored. METHODS AND RESULTS: Study participants were 815 consecutive asymptomatic participants who underwent a health screening program that included FDG positron emission tomography/computed tomography (PET/CT), abdominal ultrasonography, and carotid intima-media thickness (CIMT) measurements (age 51.8 ± 6.0 year; males 93.9%). We measured hepatic FDG uptake and assessed the prognostic significance of this parameter with other cardiovascular risk factors including Framingham risk score and CIMT. Multivariate Cox proportional hazards analyses including all study participants revealed that NAFLD with high-hepatic FDG uptake was the only independent predictor for future cardiovascular events [hazard ratio (HR) 4.23; 95% CI 1.05-17.04; P = .043). Subgroup analysis conducted in the NAFLD group showed that high-hepatic FDG uptake was a significant independent predictor of cardiovascular events (HR 9.29; 95% CI 1.05-81.04; P = .045). CONCLUSIONS: This exploratory study suggests that high-hepatic FDG uptake may be a useful prognostic factor for cardiovascular events in individuals with NAFLD.

Carotid FDG Uptake Improves Prediction of Future Cardiovascular Events in Asymptomatic Individuals.

OBJECTIVES: This study sought to investigate the role of carotid fluoro-2-deoxyglucose (FDG) uptake as an independent prognostic indicator and to determine whether its addition improves risk prediction beyond the Framingham risk score (FRS) and carotid intima-media thickness (CIMT). BACKGROUND: The prognostic value of carotid FDG uptake independent of and incremental to traditional cardiovascular risk factors and CIMT in asymptomatic individuals has not been evaluated. METHODS: We measured carotid FDG uptake and CIMT in 1,089 asymptomatic adults (51.8 ± 6.3 years of age, 94.3% males) who underwent positron emission tomography/computed tomography imaging and examined the prognostic value of carotid FDG uptake compared with traditional risk factors and CIMT. RESULTS: Cardiocerebrovascular events occurred in 19 participants (1.74%) during an average follow-up of 4.2 years (range 1.0 to 5.5 years). Multivariable Cox proportional hazards analyses revealed that high carotid FDG uptake (hazard ratio: 2.98; 95% confidence interval: 1.17 to 7.62; p = 0.022) and high CIMT (hazard ratio: 2.82; 95% confidence interval: 1.13 to 7.03; p = 0.026) were independent predictors of events. Comparison of predictive power demonstrated that adding carotid FDG uptake, but not CIMT, to the FRS significantly increased the time-dependent area under the receiver-operating characteristic curve from 0.60 to 0.73 (p = 0.04). Furthermore, improvement approaching significance was achieved by adding carotid FDG uptake to the FRS plus CIMT, which increased the area under the receiver-operating characteristic curve from 0.65 to 0.75 (p = 0.07). Net reclassification for event prediction was similarly improved by addition of carotid FDG uptake to the FRS (net reclassification index, 40.1%; p = 0.06), as well as the FRS plus CIMT (net reclassification index, 32.9%; p = 0.07). CONCLUSIONS: High carotid FDG uptake predicts cardiovascular events independent of traditional risk factors and CIMT in asymptomatic adults and may add to risk stratification beyond the FRS and CIMT.

Difference in Tinnitus Treatment Outcome According to the Pulse Number of Repetitive Transcranial Magnetic Stimulation.

OBJECTIVE: We aimed to compare the treatment result between 6,000 and 12,000 pulses of low-frequency repetitive transcranial magnetic stimulation (rTMS) and to evaluate the correct location of rTMS in Korean brains compared with that of Caucasians. STUDY DESIGN: Controlled trial. SETTING: Tertiary referral center. PATIENTS: Fourteen patients with chronic essential tinnitus were treated with rTMS on the left auditory cortex (AC) and prefrontal cortex (FC). AC targets were determined using the 10-20 electroencephalographic (EEG) method proposed by Langguth in 2006. Six patients received a total of 6,000 pulses rTMS (AC, 1,000; FC, 1,000; 3-d course; Group 1), and eight patients were given 12,000 pulses (AC, 2,000; FC, 1,000; 4-d course; Group 2). MAIN OUTCOME MEASURES: Treatment results were assessed with pretreatment and posttreatment Tinnitus Handicap Inventory (THI) and self-rating Visual Analog Scale (VAS) of awareness, loudness, annoyance, and effect on daily life of tinnitus at 1, 2, 4, 8, and 12 weeks after treatment. Using the individual subject's magnetic resonance image and Neuronavigation System, the location of primary AC was determined and compared with that of the 10-20 method in four patients. RESULTS: There was no improvement of THI and VAS in Group 1. On the contrary, a substantial decrease of THI scores and VAS scores for awareness, loudness, and effect on daily life was observed in Group 2. CONCLUSION: Despite the small number of patients, a beneficial effect of rTMS on tinnitus suppression was found in the 12,000-pulse treatment group, whereas no effect was found in the 6,000-pulse treatment group. rTMS localization based on the 10-20 EEG method seems to be valid even in Koreans with a shorter anteroposterior skull diameter.

Association between nonalcoholic fatty liver disease and carotid artery inflammation evaluated by 18F-fluorodeoxyglucose positron emission tomography.

We assessed the association between nonalcoholic fatty liver disease (NAFLD) and carotid artery inflammation measured by (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography. Participants were 755 consecutive otherwise healthy adult males who underwent a general health screening program. Carotid FDG uptake, represented as maximum target-to-background ratio, was increased with mild (n = 237; 1.61 ± 0.14; P = .033) and moderate NAFLD (n = 145; 1.63 ± 0.16; P = .005) compared with controls (n = 373; 1.58 ± 0.15). In patients aged >50 years, moderate NAFLD was the only independent risk factor for high carotid FDG uptake (odds ratio, 2.12; 95% confidence interval, 1.10-4.07; P = .001). Apparently healthy adult males with NAFLD have elevated carotid FDG uptake as well as increased carotid intima-media thickness, suggesting that they may be at an increased risk of having inflammatory atherosclerotic plaques in the carotid arteries.

Hepatic glucose uptake is increased in association with elevated serum γ-glutamyl transpeptidase and triglyceride.

BACKGROUND: Subjects with fatty liver disease (FLD) can show increased hepatic 2-deoxy-2-((18)F)fluoro-D-glucose (FDG) uptake, but the role of hepatic inflammation has not been explored. AIMS: We investigated whether hepatic inflammatory response, as implicated by elevated serum markers, is associated with increased liver FDG uptake in FLD. METHODS: Liver sonography and FDG positron emission tomography was performed in 331 asymptomatic men with nonalcoholic FLD (NAFLD), 122 with alcoholic FLD (AFLD), and 349 controls. Mean standard uptake value (SUV) of liver FDG uptake was compared to cardiac risk factors and serum markers of liver injury. RESULTS: Hepatic FDG mean SUV was increased in NAFLD (2.40 ± 0.25) and AFLD groups (2.44 ± 0.25) compared to controls (2.28 ± 0.26; both P < 0.001). Both FLD groups also had higher serum γ-glutamylranspeptidase (GGT), triglyceride (TG), hepatic transaminases, and LDL. High GGT and TG levels were independent determinants of increased FDG uptake for both FLD groups. Hepatic mean SUV significantly increased with high compared to low GGT for NAFLD (2.48 ± 0.28 vs. 2.37 ± 0.24), AFLD (2.51 ± 0.27 vs. 2.39 ± 0.23), and control groups (2.39 ± 0.22 vs. 2.26 ± 0.26). High TG increased hepatic mean SUV in AFLD and control groups. Furthermore, serum GGT and TG levels significantly correlated to hepatic mean SUV in all three groups. CONCLUSIONS: Hepatic FDG uptake is closely associated with elevated TG and GGT regardless of the presence of FLD. Thus, inflammation response may play a major role in increased hepatic glucose uptake.

Relation of carotid artery 18F-FDG uptake to C-reactive protein and Framingham risk score in a large cohort of asymptomatic adults.

UNLABELLED: We investigated the relation of carotid (18)F-FDG uptake to high-sensitivity C-reactive protein (hsCRP) and Framingham risk score (FRS) in a large cohort of asymptomatic adults. METHODS: Carotid artery (18)F-FDG uptake was measured on the PET/CT scans of 1,181 asymptomatic subjects, and maximum target-to-background ratio (M-TBR) and intima-media thickness (IMT) were compared with clinical risk factors and hsCRP. The estimated 10-y risk for general cardiovascular disease was calculated by FRS. RESULTS: FRS increased from 11.5% ± 7.8% to 14.8% ± 10.5% in subjects with an M-TBR ≥ 1.7, compared with < 1.7, and the odds ratio for an FRS ≥ 10% was 1.9 (95% confidence interval [CI], 1.4-2.5). Adjusting for age confirmed a significant association of M-TBR and IMT with FRS. Independent determinants of high M-TBR were abdominal fat (ß coefficient [B], 1.1040; P < 0.0001), low-density lipoprotein (LDL) (B, 0.0006; P < 0.05), and FRS (B, 0.0025; P < 0.05) for subjects < 50 y and abdominal fat (B, 0.9740; P < 0.0001), age (B, 0.0040; P = 0.0001), LDL (B, 0.0008; P = 0.0001), and IMT (B, 0.1097; P < 0.01) for subjects ≥ 50 y. Although hsCRP also stratified subjects for FRS-based risk, no correlation was found between hsCRP and M-TBR or IMT, suggesting that they may have different inferences. Importantly, in the low-hsCRP (14.2% ± 9.7% vs. 11.3% ± 7.4%) and high-hsCRP groups (18.8% ± 14.3% vs. 13.3% ± 10.2%), FRS was significantly greater for subjects with high M-TBR than for those with low M-TBR. The odds ratio for FRS ≥ 10% between subjects with high and low M-TBR was 1.20 (95% CI, 0.90-1.60; P = 0.209) in the low-hsCRP group and 2.95 (95% CI, 1.48-5.86; P = 0.002) in the high-hsCRP group. CONCLUSION: High carotid (18)F-FDG uptake in asymptomatic adults is associated with increased clinical risk factors and FRS. Furthermore, it appears to reflect aspects of atherosclerotic inflammation distinct from hsCRP concentration and may offer incremental information regarding cardiovascular risk.

Effects of coverage extent and slice skipping on mean and maximum arterial 18F-FDG uptake ratios in patients with carotid plaque.

PURPOSE: To investigate the effects of variable measurement methods on mean and maximum SUV ratios of 18F-FDG uptake in carotid arteries. METHODS: 18F-FDG PET/CT images of 74 subjects with carotid plaque were analyzed for mean and maximum target-to-background ratio (TBR) of uptake. Agreement was analyzed between TBR scores obtained using different vessel coverage and slice skipping. RESULTS: Mean TBR was increased by extending coverage from common carotid artery (CCA; 1.25) to carotid artery (CA; 1.33) and inclusion of ascending aorta (CA/AA; 1.34). Maximum TBR was increased from 1.47 to 1.54 and 1.61 by respective extensions. Both mean and maximum TBR were closely correlated between vessels. ICC and Kappa statistics revealed near perfect agreement between TBR obtained using every 2 or 3 segments and that without sipping. Bland-Altman plots showed bias by slice skipping to remain small, particularly for mean TBR. Finally, high correlations were displayed between mean and maximum TBR. CONCLUSIONS: Analysis of mean and maximum arterial 18F-FDG uptake in patients with carotid plaque is likely to benefit from extending coverage to segments above and below the CCA. The extra burden of measurement, in turn, can be lightened by skipping up to every 2 of 3 slices without compromising accuracy of results.