Development, initial validation, and application of a visual read method for [18F]MK-6240 tau PET.

Background: The positron emission tomography (PET) radiotracer [18F]MK-6240 exhibits high specificity for neurofibrillary tangles (NFTs) of tau protein in Alzheimer's disease (AD), high sensitivity to medial temporal and neocortical NFTs, and low within-brain background. Objectives were to develop and validate a reproducible, clinically relevant visual read method supporting [18F]MK-6240 use to identify and stage AD subjects versus non-AD and controls. Methods: Five expert readers used their own methods to assess 30 scans of mixed diagnosis (47% cognitively normal, 23% mild cognitive impairment, 20% AD, 10% traumatic brain injury) and provided input regarding regional and global positivity, features influencing assessment, confidence, practicality, and clinical relevance. Inter-reader agreement and concordance with quantitative values were evaluated to confirm that regions could be read reliably. Guided by input regarding clinical applicability and practicality, read classifications were defined. The readers read the scans using the new classifications, establishing by majority agreement a gold standard read for those scans. Two naïve readers were trained and read the 30-scan set, providing initial validation. Inter-rater agreement was further tested by two trained independent readers in 131 scans. One of these readers used the same method to read a full, diverse database of 1842 scans; relationships between read classification, clinical diagnosis, and amyloid status as available were assessed. Results: Four visual read classifications were determined: no uptake, medial temporal lobe (MTL) only, MTL and neocortical uptake, and uptake outside MTL. Inter-rater kappas were 1.0 for the naïve readers gold standard scans read and 0.98 for the independent readers 131-scan read. All scans in the full database could be classified; classification frequencies were concordant with NFT histopathology literature. Discussion: This four-class [18F]MK-6240 visual read method captures the presence of medial temporal signal, neocortical expansion associated with disease progression, and atypical distributions that may reflect different phenotypes. The method demonstrates excellent trainability, reproducibility, and clinical relevance supporting clinical use. Highlights: A visual read method has been developed for [18F]MK-6240 tau positron emission tomography.The method is readily trainable and reproducible, with inter-rater kappas of 0.98.The read method has been applied to a diverse set of 1842 [18F]MK-6240 scans.All scans from a spectrum of disease states and acquisitions could be classified.Read classifications are consistent with histopathological neurofibrillary tangle staging literature.

Central Review of Amyloid-Related Imaging Abnormalities in Two Phase III Clinical Trials of Bapineuzumab in Mild-To-Moderate Alzheimer's Disease Patients.

BACKGROUND: Amyloid-related imaging abnormalities (ARIA) consist of ARIA-E (with effusion or edema) and ARIA-H (hemosiderin deposits [HDs]). OBJECTIVES: To address accurate ascertainment of ARIA identification, a final magnetic resonance imaging (MRI) reading was performed on patients with mild-to-moderate Alzheimer's disease randomized to bapineuzumab IV or placebo during two Phase III trials (APOE ɛ4 allele carriers or noncarriers). METHODS: Final MRI central review consisted of a systematic sequential locked, adjudicated read in 1,331 APOE ɛ4 noncarriers and 1,121 carriers by independent neuroradiologists. Assessment of ARIA-E, ARIA-H, intracerebral hemorrhages, and age-related white matter changes is described. RESULTS: In the Final Read, treatment-emergent ARIA-E were identified in 242 patients including 76 additional cases not noted previously in real time. Overall, incidence proportion of ARIA-E was higher in carriers (active 21.2%; placebo 1.1%) than in noncarriers (pooled active 11.3%; placebo 0.6%), and was more often identified in homozygote APOE ɛ4 carriers than heterozygotes (34.5% versus 16.9%). Incidence rate of ARIA-E increased with increased dose in noncarriers. Frequency of ARIA-E first episodes was highest after the first and second bapineuzumab infusion and declined after repeated infusions. Incidence of total HDs <10 mm (cerebral microhemorrhages) was higher in active groups versus placebo. CONCLUSION: ARIA was detected more often on MRI scans when every scan was reviewed by trained neuroradiologists and results adjudicated. There was increased incidence of ARIA-E in bapineuzumab-treated carriers who had a microhemorrhage at baseline. ARIA-E was a risk factor for incident ARIA-H and late onset ARIA-E was milder radiologically. Age-related white matter changes did not progress during the study.

Validation of an MRI Rating Scale for Amyloid-Related Imaging Abnormalities.

INTRODUCTION: Immunotherapeutic agents against amyloid beta (Aß) are associated with adverse events, including amyloid-related imaging abnormalities with edema and effusion (ARIA-E). Recently, a magnetic resonance imaging (MRI) rating scale was developed for ARIA-E detection and classification. The aim of this study was to validate the use of this rating scale in a larger patient group with multiple raters. METHODS: MRI scans of 75 patients (29 with known ARIA-E and 46 control subjects) were analyzed by five neuroradiologists with different degrees of expertise, according to the ARIA-E rating scale. For each patient, we included a baseline and a follow-up fluid-attenuated inversion recovery image. Interrater agreement was calculated using intraclass correlation coefficient (ICC). RESULTS: On average, 4.1% of the ARIA-E cases were missed. We observed a high interrater agreement for scores of sulcal hyperintensity (SH; ICC = .915; 95% CI 85-95) and for the combined scores of the 2 ARIA-E findings, parenchymal hyperintensity (PH) and SH (ICC = .878; 95% CI 79-93). A slightly lower agreement for PH (ICC = .678; 95% CI 51-81) was noted. CONCLUSION: The ARIA-E rating scale is a simple tool to evaluate the extent of ARIA-E in patients recruited into Aß-lowering therapeutic trials. It shows high interrater agreement among raters with different degrees of expertise.

Benign anterior temporal epidural hematoma: indolent lesion with a characteristic CT imaging appearance after blunt head trauma.

PURPOSE: To study the incidence, pathogenesis, imaging characteristics, and clinical importance of a unique subtype of epidural hematoma (EDH) associated with blunt head trauma. MATERIALS AND METHODS: This study was reviewed and approved by the hospital's Institutional Review Board and was compliant with HIPAA. Informed consent was waived. The investigation was a retrospective study of 200 patients with acute supratentorial EDH, defined as a biconvex, high-attenuating, extraaxial hematoma. A subgroup of 21 patients in whom the EDH was located at the anterior aspect of the middle cranial fossa was defined. Computed tomographic images and inpatient medical records of these 21 patients were evaluated for imaging characteristics of the EDH, presence or absence of associated fracture, presence or absence of midline shift and/or mass effect, additional intracranial injury, and hospital clinical course. RESULTS: Twenty-one (10.5%) of 200 traumatic EDHs localized to the anterior middle cranial fossa. All of these 21 anterior temporal EDHs were juxtaposed to the sphenoparietal sinus, and all but one were limited laterally by the sphenotemporal suture and medially by the orbital fissure; none extended above the lesser sphenoid wing. Maximum thickness was less than 1 cm in 13 (62%) of 21 and less than 2 cm in 20 (95%) of 21 patients. Isolated fractures of the greater sphenoid wing and ipsilateral zygomaticomaxillary fractures were present in 12 (57%) of 21 and nine (43%) of 21 patients, respectively. Concomitant intracranial injury was identified in 15 (71%) of 21 patients. Twenty (95%) of 21 lesions were present at the admission study, and all 21 were stable or smaller at follow-up imaging. No patient required neurosurgical intervention of their anterior temporal EDH. CONCLUSION: Acute EDHs isolated to the anterior aspect of the middle cranial fossa constitute a subgroup of traumatic EDHs with a benign natural history. It is postulated that they arise from venous bleeding due to disruption of the sphenoparietal sinus.

Evaluation of intracranial stenoses and aneurysms with accelerated 4D flow.

The aim of this study was to evaluate intracranial arterial stenoses and aneurysms with accelerated time-resolved three-dimensional (3D) phase-contrast MRI or 4D flow. The 4D flow technique was utilized to image four normal volunteers, two patients with intracranial stenoses and two patients with intracranial aneurysms. In order to reduce scan time, parallel imaging was combined with an acquisition strategy that eliminates the corners of k-space. In the two patients with intracranial stenoses, 4D flow velocity measurements showed that one patient had normal velocity profiles in agreement with a previous magnetic resonance angiogram (MRA), while the second showed increased velocities that indicated a less significant narrowing than suspected on a previous MRA, as confirmed by catheter angiography. This result may have prevented an invasive angiogram. In the two patients with 4-mm intracranial aneurysm, one had a stable helical flow pattern with a large jet, while the other had a temporally unstable flow pattern with a more focal jet possibly indicating that the second aneurysm may have a higher likelihood of rupture. Accelerated 4D flow provides time-resolved 3D velocity data in an 8- to 10-min scan. In the stenosis patients, the addition of 4D flow to a traditional MRA adds the velocity data provided from transcranial Doppler ultrasound (TCD) possibly allowing for more accurate grading of stenoses. In the aneurysm patients, visualization of flow patterns may help to provide prognostic information about future risk of rupture.

Improved fluorescence of indocyanine green in vitro and in vivo after simple cooling procedures.

Indocyanine green (ICG) is a contrast agent used for detecting angiogenesis with optical imaging (OI). The purpose of this study was to investigate whether cooling procedures increase the signal yield of ICG with OI. Test samples of 0.05 and 0.02 mM ICG in 40% DMSO and 60% DMEM underwent OI at four different temperatures (5, 37, 55 and 75 degrees C). In addition, six athymic rats with an antigen-induced arthritis of the knee and ankle joints underwent OI before and after injection of ICG (10 mg/ml, dose 15 mg/kg) on two separate days with and without cooling of the joints. The fluorescent signals of the test samples and arthritic joints were measured and evaluated for significant differences before and after cooling with a t-test. In vitro studies showed a strong negative correlation between ICG temperature and fluorescent signal. The mean fluorescent signal of arthritic joints (measured in efficiency) was 0.345 before ICG-injection, 4.55 after ICG-injection and before cooling and 9.71 after ICG-injection and after cooling. The fluorescent signal enhancement of arthritic joints with ICG-enhanced OI images increased significantly after cooling (p = 0.02). The signal yield of ICG can be significantly increased by cooling the target pathology. The primary underlying cause of the temperature dependence of ICG is enhanced collisional quenching with increasing temperature. This simple cooling method may be immediately helpful to increase the fluorescence signal yield in current ICG-enhanced OI-studies in patients.

High-resolution intracranial MRA at 7T using autocalibrating parallel imaging: initial experience in vascular disease patients.

PURPOSE: Greater spatial resolution in intracranial three-dimensional time-of-flight (TOF) magnetic resonance angiography (MRA) is possible at higher field strengths, due to the increased contrast-to-noise ratio (CNR) from the higher signal-to-noise ratio and the improved background suppression. However, at very high fields, spatial resolution is limited in practice by the acquisition time required for sequential phase encoding. In this study, we applied parallel imaging to 7T TOF MRA studies of normal volunteers and patients with vascular disease, in order to obtain very high resolution (0.12 mm(3)) images within a reasonable scan time. MATERIALS AND METHODS: Custom parallel imaging acquisition and reconstruction methods were developed for 7T MRA, based on generalized autocalibrating partially parallel acquisition (GRAPPA). The techniques were compared and applied to studies of seven normal volunteers and three patients with cerebrovascular disease. RESULTS: The technique produced high resolution studies free from discernible reconstruction artifacts in all subjects and provided excellent depiction of vascular pathology in patients. CONCLUSIONS: 7T TOF MRA with parallel imaging is a valuable noninvasive angiographic technique that can attain very high spatial resolution.

Recording, editing, archiving, and distributing radiology lectures: a streamlined approach.

Recent advances in digital recording technology have simplified the recording of audio, video, and image information from didactic radiology conferences. Recording lectures in a suitable digital format has several advantages, including the ability to edit lecture content, combine lectures conducted at different times and places, store media digitally, and broadcast conferences electronically over the Internet. An inexpensive, commercially available conversion device was developed that allows straightforward capture and compression of multimedia audiovisual information, thus facilitating the use of this information by the conference presenter as well as the end user. A converter is connected to a personal computer (PC) by means of standard connections, and editing and compression of digital media are performed on the PC prior to their distribution and archiving. The result is a high-quality, highly compressed file that can be played back from any PC and from many portable video devices. This approach represents a simple and cost-effective means of creating and maintaining a library of didactic lectures for students and trainees in radiology.

Intracranial time-of-flight MR angiography at 7T with comparison to 3T.

PURPOSE: To establish the feasibility of intracranial time-of-flight (TOF) MR angiography (MRA) at 7T using phased array coils and to compare its performance to 3T. MATERIALS AND METHODS: In an initial study, five normal volunteers were scanned at 7T and 3T using eight-channel coils and standard acquisition parameters from a clinical TOF protocol. In a second study three additional studies were performed at 7T and 3T using empirically optimized 7T parameters. Contrast-to-noise (CNR) values were measured for major vessel segments. RESULTS: All measurements documented CNR increases at 7T, with a mean increase of 83% in the initial study and 88% in the second study. The CNR values achieved using the latter protocol were similar to the values obtained in the initial study, despite the 42% reduction expected due to the higher spatial resolution. CNR in the smaller peripheral vessels was increased dramatically, resulting in excellent visualization at high resolution. CONCLUSION: TOF MRA at 7T demonstrated improved visualization of the intracranial vasculature, particularly the smaller peripheral vessels, and may benefit studies of small aneurysms, atherosclerosis, vasospasm, and vasculitis.

Anterior layering of excreted 18F-FDG in the bladder on PET/CT: frequency and cause.

OBJECTIVE: The objective of our study was to determine the frequency and cause of anterior layering of excreted 18F-FDG in the bladder on PET/CT. CONCLUSION: Anterior layering of excreted FDG in the bladder is commonly seen on PET/CT scans obtained with i.v. iodinated contrast material and is due to displacement of FDG by excreted iodinated contrast material; this phenomenon may unmask FDG-avid bladder disease.

Two temporal bone computed tomography measurements increase recognition of malformations and predict sensorineural hearing loss.

OBJECTIVES/HYPOTHESIS: The objectives of this prospective study were to assess the reproducibility of the measurements of the cochlea and lateral semicircular canal (LSCC) and to determine if abnormal measurements predict sensorineural hearing loss (SNHL). METHODS: Two readers independently measured the cochlear height on coronal section and the LSCC bony island width on axial section on 109 temporal bone computed tomography scans; audiologic data on these patients were collected independently from medical records. Inter- and intrareader variability was evaluated using intraclass correlation coefficients (ICCs) based on a random-effects model. The positive and negative predictive values of abnormal measurement for hearing loss were determined. RESULTS: There was excellent inter- and intraobserver agreement for both measurements (ICC >80%). The average cochlear height was 5.1 mm (normal range, 4.4-5.9 mm) and average LSCC bony island width was 3.7 mm (normal range, 2.6-4.8 mm). Review of the original radiology reports demonstrated that both cochlear hypoplasia and LSSC dysplasia were overlooked in >50% of patients with both abnormal measurements and SNHL. Cochlear hypoplasia (< 4.4 mm) had a positive predictive value of 100% for SNHL, whereas cochlear hyperplasia and bony island dysplasia were less predictive. CONCLUSION: The measurements of coronal cochlear height and axial LSCC bony width have excellent reproducibility and identify bony labyrinth abnormalities missed by visual inspection alone. In addition, cochlear hypoplasia is highly predictive of SNHL. To reliably identify inner ear malformations, measurement of the cochlear height and LSCC bony island width, in addition to the vestibular aqueduct, should be routinely performed on all temporal bone studies.

Identification of previously "undetectable" abnormalities of the bony labyrinth with computed tomography measurement.

BACKGROUND: In patients with congenital sensorineural hearing loss (SNHL), a computed tomography (CT) scan of the temporal bone identifies inner ear malformations in approximately 25%, whereas the inner ear is grossly normal to visual inspection in the remaining 75% of the patients. In the latter group, the hearing loss is often attributed to radiologically undetectable abnormalities of the membranous labyrinth. However, subtle bony malformations may be missed because visual inspection alone is insensitive for detection. OBJECTIVE: To test the hypothesis that there are subtle bony abnormalities of the inner ear in patients with SNHL who are radiologically deemed to have normal otic bone, using standardized measurements of the inner ear. STUDY DESIGN: Retrospective review. METHODS: Measurements of the cochlea, vestibule, and semicircular canals (SCCs) were made on axial and coronal temporal bone CT scans on 15 patients with normal hearing and 15 patients with congenital SNHL and grossly normal temporal bone CT scans. Student's t-test was performed to compare the measurements of the two groups. RESULTS All studies from the SNHL group were deemed normal by visual inspection and standardized measurements (+/-2 SD from normal). Surprisingly, there were significant differences in the measurements of the cochlea and of the SCCs between patients with and without SHNL (P <.05). CONCLUSIONS: As a group, patients with SNHL and a "normal CT scan" have significant differences in the dimensions of the inner ear. This suggests that these patients have disturbed morphogenesis of both membranous and bony labyrinth. This novel observation has important implications for understanding the etiology of SNHL.