What is the added value of specialist radiology review of multidisciplinary team meeting cases in a tertiary care center?

PURPOSE: Multidisciplinary team meetings (MDTMs) are an important component of the workload of radiologists. This study investigated how often subspecialized radiologists change patient management in MDTMs at a tertiary care institution. MATERIALS AND METHODS: Over 2 years, six subspecialty radiologists documented their contributions to MDTMs at a tertiary care center. Both in-house and external imaging examinations were discussed at the MDTMs. All imaging examinations (whether primary or second opinion) were interpreted and reported by subspecialty radiologist prior to the MDTMs. The management change ratio (MCratio) of the radiologist was defined as the number of cases in which the radiologist's input in the MDTM changed patient management beyond the information that was already provided by the in-house (primary or second opinion) radiology report, as a proportion of the total number of cases whose imaging examinations were prepared for demonstration in the MDTM. RESULTS: Sixty-eight MDTMs were included. The time required for preparing and attending all MDTMs (excluding imaging examinations that had not been reported yet) was 11,000 min, with a median of 172 min (IQR 113-200 min) per MDTM, and a median of 9 min (IQR 8-13 min) per patient. The radiologists' input changed patient management in 113 out of 1138 cases, corresponding to an MCratio of 8.4%. The median MCratio per MDTM was 6% (IQR 0-17%). CONCLUSION: Radiologists' time investment in MDTMs is considerable relative to the small proportion of cases in which they influence patient management in the MDTM. The use of radiologists for MDTMs should therefore be improved. CLINICAL RELEVANCE STATEMENT: The use of radiologists for MDTMs (multidisciplinary team meetings) should be improved, because their time investment in MDTMs is considerable relative to the small proportion of cases in which they influence patient management in the MDTM. KEY POINTS: • Multidisciplinary team meetings (MDTMs) are an important component of the workload of radiologists. • In a tertiary care center in which all imaging examinations have already been interpreted and reported by subspecialized radiologists before the MDTM takes place, the median time investment of a radiologist for preparing and demonstrating one MDTM patient is 9 min. • In this setting, the radiologist changes patient management in only a minority of cases in the MDTM.

Focused view CT angiography for selective visualization of stroke related arteries: technical feasibility.

OBJECTIVES: This study investigated the technical feasibility of focused view CTA for the selective visualization of stroke related arteries. METHODS: A total of 141 CTA examinations for acute ischemic stroke evaluation were divided into a set of 100 cases to train a deep learning algorithm (dubbed "focused view CTA") that selectively extracts brain (including intracranial arteries) and extracranial arteries, and a test set of 41 cases. The visibility of anatomic structures at focused view and unmodified CTA was assessed using the following scoring system: 5 = completely visible, diagnostically sufficient; 4 = nearly completely visible, diagnostically sufficient; 3 = incompletely visible, barely diagnostically sufficient; 2 = hardly visible, diagnostically insufficient; 1 = not visible, diagnostically insufficient. RESULTS: At focused view CTA, median scores for the aortic arch, subclavian arteries, common carotid arteries, C1, C6, and C7 segments of the internal carotid arteries, V4 segment of the vertebral arteries, basilar artery, cerebellum including cerebellar arteries, cerebrum including cerebral arteries, and dural venous sinuses, were all 4. Median scores for the C2 to C5 segments of the internal carotid arteries, and V1 to V3 segments of the vertebral arteries ranged between 3 and 2. At unmodified CTA, median score for all above-mentioned anatomic structures was 5, which was significantly higher (p < 0.0001) than that at focused view CTA. CONCLUSION: Focused view CTA shows promise for the selective visualization of stroke-related arteries. Further improvements should focus on more accurately visualizing the smaller and tortuous internal carotid and vertebral artery segments close to bone. CLINICAL RELEVANCE: Focused view CTA may speed up image interpretation time for LVO detection and may potentially be used as a tool to study the clinical relevance of incidental findings in future prospective long-term follow-up studies. KEY POINTS: • A deep learning-based algorithm ("focused view CTA") was developed to selectively visualize relevant structures for acute ischemic stroke evaluation at CTA. • The elimination of unrequested anatomic background information was complete in all cases. • Focused view CTA may be used to study the clinical relevance of incidental findings.

Susceptibility-weighted imaging in intracranial hemorrhage: not all bleeds are black.

To correctly recognize intracranial hemorrhage (ICH) and differentiate it from other lesions, knowledge of the imaging characteristics of an ICH on susceptibility weighted imaging (SWI) is essential. It is a common misconception that blood is always black on SWI, and it is important to realize that hemorrhage has a variable appearance in different stages on SWI. Furthermore, the presence of a low signal on SWI does not equal the presence of blood products. In this review, the appearance of ICH on SWI during all its stages and common other causes of a low signal on SWI are further discussed and illustrated.

Spatial distribution of cerebral microbleeds and FLAIR hyperintensities on follow-up MRI after radiotherapy for lower grade glioma.

Background and purpose: Cerebral microbleeds (CMBs) and fluid-attenuated-inversion recovery (FLAIR) hyperintensities on brain MRI scans after radiotherapy (RT) are considered markers for microvascular damage and related cognitive changes. However, the spatial distribution using existing scoring systems as well as colocation of these imaging biomarkers remain unclear, hampering clinical interpretation. This study aims to elucidate the distribution and colocation of these markers in patients with lower grade glioma (LGG). Materials and methods: CMBs were spatially classified on retrospective 1.5 T susceptibility weighted MRI scans according to the existing Microbleed Anatomical Rating Scale (MARS) and were additionally scored for being located in hippocampus, amygdala, cortex, white matter (WM), grey matter (GM), WM/GM junction and for their spatial relation to FLAIR hyperintensities. Scoring was performed for whole, ipsilateral and contralateral cerebrum (with respect to tumour bulk). Results: Fifty-one scans were included of which 28 had at least one CMB. The majority of CMBs were localized in the lobar area and in deep and periventricular white matter (DPWM) - generally in WM. Only few CMBs were found in GM. In scans obtained up to 7 years after RT completion the majority of CMBs were not colocalized with FLAIR hyperintensities. Conclusion: CMBs and FLAIR hyperintensities appear to be separate imaging biomarkers for radiation therapy induced microvascular damage, as they are not colocalized in patients with LGG, especially not early on after completion of RT.

Primary Cauda Equina T-Cell Lymphoblastic Lymphoma.

BACKGROUND: T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive form of non-Hodgkin lymphoma. This report describes, to our knowledge, the first adult case of a primary cauda equina T-LBL. Treatment consists of multiagent chemotherapy, and surgical removal of T-LBL does not improve outcome. We discuss the workup of patients with an intradural spinal mass, together with a review of the literature on primary spinal lymphoma of the cauda equina. CASE DESCRIPTION: A 54-year-old woman with Crohn's disease, for which she was taking immunosuppressive medication, presented with progressive back pain radiating to both legs and deteriorating neurologic deficits caused by an intradural, contrast-enhancing lesion in the L1-5 region. During acute surgery, the tumor was partially resected. Immunohistochemical phenotyping revealed a T-LBL. No other lymphoma localizations were found after subsequent staging. Despite extensive treatment, the patient died of disseminated disease throughout the central nervous system, 6 weeks after the diagnosis. CONCLUSIONS: Pain and progressive neurologic complaints can be symptoms of a (malignant) intradural spinal tumor. Intradural lymphoma must be considered as a differential diagnosis by clinicians because it can mimic neoplasms that often require urgent surgery. The histopathologic diagnosis should preferably be obtained by way of cerebrospinal fluid analysis or tumor biopsy because tumor resection has no beneficial effect on the oncologic outcome.

Amyloid imaging of dutch-type hereditary cerebral amyloid angiopathy carriers.

OBJECTIVE: To determine whether amyloid imaging with the positron emission tomography (PET) agent Pittsburgh compound B (PiB) can detect vascular ß-amyloid (Aß) in the essentially pure form of cerebral amyloid angiopathy associated with the Dutch-type hereditary cerebral amyloid angiopathy (D-CAA) mutation. METHODS: PiB retention in a cortical composite of frontal, lateral, and retrosplenial regions (FLR) was measured by PiB-PET in 19 D-CAA mutation carriers (M+ ; 13 without neurologic symptoms, 6 with prior lobar intracerebral hemorrhage) and 17 mutation noncarriers (M- ). Progression of PiB retention was analyzed in a subset of 18 serially imaged individuals (10 asymptomatic M+ , 8 M- ). We also analyzed associations between PiB retention and cerebrospinal fluid (CSF) Aß concentrations in 17 M+ and 11 M- participants who underwent lumbar puncture and compared the findings to PiB-PET and CSF Aß in 37 autosomal dominant Alzheimer disease (ADAD) mutation carriers. RESULTS: D-CAA M+ showed greater age-dependent FLR PiB retention (p < 0.001) than M- , and serially imaged asymptomatic M+ demonstrated greater longitudinal increases (p = 0.004). Among M+ , greater FLR PiB retention associated with reduced CSF concentrations of Aß40 (r = -0.55, p = 0.021) but not Aß42 (r = 0.01, p = 0.991). Despite comparably low CSF Aß40 and Aß42, PiB retention was substantially less in D-CAA than ADAD (p < 0.001). INTERPRETATION: Increased PiB retention in D-CAA and correlation with reduced CSF Aß40 suggest this compound labels vascular amyloid, although to a lesser degree than amyloid deposits in ADAD. Progression in PiB signal over time suggests amyloid PET as a potential biomarker in trials of candidate agents for this untreatable cause of hemorrhagic stroke. ANN NEUROL 2019;86:616-625.

Neurophysiological effects of sleep deprivation in healthy adults, a pilot study.

Total sleep deprivation (TSD) may induce fatigue, neurocognitive slowing and mood changes, which are partly compensated by stress regulating brain systems, resulting in altered dopamine and cortisol levels in order to stay awake if needed. These systems, however, have never been studied in concert. At baseline, after a regular night of sleep, and the next morning after TSD, 12 healthy subjects performed a semantic affective classification functional magnetic resonance imaging (fMRI) task, followed by a [11C]raclopride positron emission tomography (PET) scan. Saliva cortisol levels were acquired at 7 time points during both days. Affective symptoms were measured using Beck Depression Inventory (BDI), Spielberger State Trait Anxiety Index (STAI) and visual analogue scales. After TSD, perceived energy levels, concentration, and speed of thought decreased significantly, whereas mood did not. During fMRI, response speed decreased for neutral words and positive targets, and accuracy decreased trendwise for neutral words and for positive targets with a negative distracter. Following TSD, processing of positive words was associated with increased left dorsolateral prefrontal activation. Processing of emotional words in general was associated with increased insular activity, whereas contrasting positive vs. negative words showed subthreshold increased activation in the (para)hippocampal area. Cortisol secretion was significantly lower after TSD. Decreased voxel-by-voxel [11C]raclopride binding potential (BPND) was observed in left caudate. TSD induces widespread cognitive, neurophysiologic and endocrine changes in healthy adults, characterized by reduced cognitive functioning, despite increased regional brain activity. The blunted HPA-axis response together with altered [11C]raclopride binding in the basal ganglia indicate that sustained wakefulness requires involvement of additional adaptive biological systems.

Comparison of simplified parametric methods for visual interpretation of 11C-Pittsburgh compound-B PET images.

UNLABELLED: This study compared several parametric imaging methods to determine the optimal approach for visual assessment of parametric Pittsburgh compound-B ((11)C-PIB) PET images to detect cortical amyloid deposition in different memory clinic patient groups. METHODS: Dynamic (11)C-PIB scanning of 120 memory clinic patients was performed. Parametric nondisplaceable binding potential (BPND) images were compared with standardized uptake value (SUV) and SUV ratio images. Images were visually assessed by 3 independent readers, and both interreader and intermethod agreement was determined. RESULTS: Both 90-min (Fleiss κ = 0.88) and 60-min (Fleiss κ = 0.89) BPND images showed excellent interreader agreement, whereas agreement was good to moderate for SUV ratio images (Fleiss κ = 0.68) and SUV images (Fleiss κ = 0.59). Intermethod agreement varied substantially between readers, although BPND images consistently showed the best performance. CONCLUSION: The use of BPND images provided the highest interreader and intermethod agreement and is therefore the method of choice for optimal visual interpretation of (11)C-PIB PET scans.

18 F-FDG PET standard uptake values of the normal pons in children: establishing a reference value for diffuse intrinsic pontine glioma.

BACKGROUND: Positron emission tomography (PET) scanning with [18 F]fluorodeoxyglucose (18 F-FDG) is a useful diagnostic and prediction tool in brain tumors, but its value in childhood diffuse intrinsic pontine glioma (DIPG) is still unclear. For interpretation of 18 F-FDG PET results in DIPG, uptake values of the normal pons of children of increasing ages are mandatory. The aim of this study was to determine 18 F-FDG standard uptake value ratios (SUVr) of the normal pons and to compare these to those of DIPG. METHODS: We studied 36 subjects with a normal, non-affected pons (aged 5 to 23 years) and 6 patients with DIPG (aged 4 to 17 years) who underwent 18 F-FDG PET scanning. Magnetic resonance imaging (MRI) was co-registered to define the regions of interest. SUVr and SUVrmax for the pons/cerebellum (SUVrp/c) and the pons/occipital lobe (SUVrp/o) were calculated. Independent-samples t tests and Mann-Whitney U tests were used to compare the mean SUVr and Pearson's test for correlations. RESULTS: For the normal pons, mean SUVrp/c and SUVrp/o were 0.65 (±0.054) and 0.51 (±0.056), respectively. No significant correlations were found between the SUVr of the normal pons and sex, age, nor pontine volume. A modest but statistically significant correlation was found between SUVr and post-injection time acquisition timing. For DIPG, mean SUVrp/c and SUVrp/o were 0.74 (±0.20) and 0.65 (±0.30), respectively, while mean SUVrp(max)/c and SUVrp(max)/o were 1.95 (±0.48) and 1.81 (±0.20), respectively. CONCLUSION: The SUVr of the unaffected pons are strikingly constant between children, irrespective of sex and age, and can therefore be well used as a reference value for 18 F-FDG PET studies in DIPG.

In vivo measurements of blood flow and bone metabolism in osteoarthritis.

With increasing age, there may be a decrease in femoral blood flow. In some patients, this may result in local ischaemia, which subsequently may lead to local degenerative changes. Consequently, bone blood flow may play an important role in the aetiology of osteoarthritis of the hip. Little is known about bone blood flow in the femoral head of patients with advanced hip osteoarthritis. The purpose of this study was to evaluate bone blood flow and metabolism in vivo in patients with osteoarthritis of the hip. Ten patients with symptomatic osteoarthritis of the hip were enrolled prospectively. Femoral bone blood flow and metabolism were measured using positron emission tomography together with H2(15)O and [(18)F]fluoride, respectively. Blood flow was 0.054 ± 0.032 mL cm(-3) min(-1) and 0.041 ± 0.012 mL cm(-3) min(-1) in symptomatic and contralateral femoral heads, respectively (p = 0.435). The net flux of fluoride from plasma to bone mineral (K i ) was significantly (p = 0.027) higher in the femoral head of the osteoarthritic hip (0.022 ± 0.012 mL cm(-3) min(-1)) than in that of the contralateral hip (0.007 ± 0.005 mL cm(-3) min(-1)). This study showed significant increase in bone metabolism in the proximal femur of patients with symptomatic osteoarthritis of the hip joint. There was no evidence of decreased blood flow.

Microglial activation in Alzheimer's disease: an (R)-[¹¹C]PK11195 positron emission tomography study.

UNLABELLED: Inflammatory mechanisms, like microglial activation, could be involved in the pathogenesis of Alzheimer's disease (AD). (R)-[(11)C]PK11195 (1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl)-3-isoquinolinecarboxamide), a positron emission tomography (PET) ligand, can be used to quantify microglial activation in vivo. The purpose of this study was to assess whether increased (R)-[(11)C]PK11195 binding is present in AD and mild cognitive impairment (MCI), currently also known as "prodromal AD." METHODS: Nineteen patients with probable AD, 10 patients with prodromal AD (MCI), and 21 healthy control subjects were analyzed. Parametric images of binding potential (BP(ND)) of (R)-[(11)C]PK11195 scans were generated using receptor parametric mapping (RPM) with supervised cluster analysis. Differences between subject groups were tested using mixed model analysis, and associations between BP(ND) and cognition were evaluated using Pearson correlation coefficients. RESULTS: Voxel-wise statistical parametric mapping (SPM) analysis showed small clusters of significantly increased (R)-[(11)C]PK11195 BP(ND) in occipital lobe in AD dementia patients compared with healthy control subjects. Regions of interest (ROI)-based analyses showed no differences, with large overlap between groups. There were no differences in (R)-[(11)C]PK11195 BP(ND) between clinically stable prodromal AD patients and those who progressed to dementia, and BP(ND) did not correlate with cognitive function. CONCLUSION: Microglial activation is a subtle phenomenon occurring in AD.

Amyloid burden and metabolic function in early-onset Alzheimer's disease: parietal lobe involvement.

Alzheimer's disease with early onset often presents with a distinct cognitive profile, potentially reflecting a different distribution of underlying neuropathology. The purpose of this study was to examine the relationships between age and both in vivo fibrillary amyloid deposition and glucose metabolism in patients with Alzheimer's disease. Dynamic [(11)C]Pittsburgh compound-B (90 min) and static [(18)F]fluorodeoxyglucose (15 min) scans were obtained in 100 patients with Alzheimer's disease and 20 healthy controls. Parametric non-displaceable binding potential images of [(11)C]Pittsburgh compound-B and standardized uptake value ratio images of [(18)F]fluorodeoxyglucose were generated using cerebellar grey matter as reference tissue. Nine [(11)C]Pittsburgh compound-B-negative patients were excluded. The remaining patients were categorized into younger (n=45, age: 56 ± 4 years) and older (n=46, age: 69 ± 5 years) groups, based on the median age (62 years) at time of diagnosis. Younger patients showed more severe impairment on visuo-spatial function, attention and executive function composite scores (P<0.05), while we found a trend towards poorer memory performance for older patients (P=0.11). Differences between groups were assessed using a general linear model with repeated measures (gender adjusted) with age as between subjects factor, region (frontal, temporal, parietal and occipital and posterior cingulate cortices) as within subjects factor and [(11)C]Pittsburgh compound-B binding/[(18)F]fluorodeoxyglucose uptake as dependent variables. There was no main effect of age for [(11)C]Pittsburgh compound-B or [(18)F]fluorodeoxyglucose, suggesting that overall, the extent of amyloid deposition or glucose hypometabolism did not differ between groups. Regional distributions of [(11)C]Pittsburgh compound-B binding and [(18)F]fluorodeoxyglucose uptake (both P for interaction <0.05) differed between groups, however, largely due to increased [(11)C]Pittsburgh compound-B binding and decreased [(18)F]fluorodeoxyglucose uptake in the parietal cortex of younger patients (both P<0.05). Linear regression analyses showed negative associations between visuo-spatial functioning and parietal [(11)C]Pittsburgh compound-B binding for younger patients (standardized ß: -0.37) and between visuo-spatial functioning and occipital binding for older patients (standardized ß: -0.39). For [(18)F]fluorodeoxyglucose, associations were found between parietal uptake with visuo-spatial (standardized ß: 0.55), attention (standardized ß: 0.39) and executive functioning (standardized ß: 0.37) in younger patients, and between posterior cingulate uptake and memory in older patients (standardized ß: 0.41, all P<0.05). These in vivo findings suggest that clinical differences between younger and older patients with Alzheimer's disease are not restricted to topographical differentiation in downstream processes but may originate from distinctive distributions of early upstream events. As such, increased amyloid burden, together with metabolic dysfunction, in the parietal lobe of younger patients with Alzheimer's disease may contribute to the distinct cognitive profile in these patients.

Parametric [11C]flumazenil images.

OBJECTIVE: This [11C]flumazenil (FMZ) study evaluates the performance of various parametric analysis methods and their ability to detect statistically significant group differences. METHODS: Dynamic 60-min FMZ scans were performed in eight healthy and nine individuals with major depressive disorder. Parametric volume of distribution (VT) images were generated using a basis function method (BFM) implementation of the single tissue compartment model (1T) and Logan plot analysis, both with a metabolite-corrected arterial plasma input function. Parametric binding potential (BP ND) images were generated using multilinear reference tissue methods (MRTM0-4), reference Logan and receptor parametric mapping (RPM1-2), with pons as a reference region. Standardized uptake value (SUV) and SUV ratio-to-pons (SUVr) images were calculated over the time interval 30-40 and 20-60 min postinjection. The resulting VT, BP ND, SUV and SUVr values were compared with nonlinear regression values, using both the 1T model and the simplified reference tissue model. Statistical parametric mapping (SPM5) was used to detect group differences, with an emphasis on the bilateral parahippocampal gyri. RESULTS: BFM was more accurate than Logan, but showed more variability. Both RPM methods and MRTM2 showed the best average correlation with the simplified reference tissue model. In using SPM, SUV and SUVr images provided the best contrast between groups in the parahippocampal gyri, but provided large underestimation and overestimation in quantitative comparisons. BFM and RPM methods allowed for the determination of perfusion effects. CONCLUSION: Parametric Logan VT, MRTM2 and RPM1-2 BP ND methods allow the best quantitative comparison of FMZ binding between groups and show good discriminating performance in SPM analysis.

Microglial activation in healthy aging.

Healthy brain aging is characterized by neuronal loss and decline of cognitive function. Neuronal loss is closely associated with microglial activation and postmortem studies have indeed suggested that activated microglia may be present in the aging brain. Microglial activation can be quantified in vivo using (R)-[(11)C]PK11195 and positron emission tomography. The purpose of this study was to measure specific binding of (R)-[(11)C]PK11195 in healthy subjects over a wide age range. Thirty-five healthy subjects (age range 19-79 years) were included. In all subjects 60-minute dynamic (R)-[(11)C]PK11195 scans were acquired. Specific binding of (R)-[(11)C]PK11195 was calculated using receptor parametric mapping in combination with supervised cluster analysis to extract the reference tissue input function. Increased binding of (R)-[(11)C]PK11195 with aging was found in frontal lobe, anterior and posterior cingulate cortex, medial inferior temporal lobe, insula, hippocampus, entorhinal cortex, thalamus, parietal and occipital lobes, and cerebellum. This indicates that activated microglia appear in several cortical and subcortical areas during healthy aging, suggesting widespread neuronal loss.

Macrophage positron emission tomography imaging as a biomarker for preclinical rheumatoid arthritis: findings of a prospective pilot study.

OBJECTIVE: To conduct a prospective pilot study to determine whether macrophage targeting by 11C-(R)-PK11195 positron emission tomography (PET) can visualize subclinical synovitis in arthralgia patients who have anti-citrullinated protein antibodies (ACPAs). METHODS: Twenty-nine arthralgia patients who were positive for ACPAs but did not have clinical arthritis were studied. High (spatial)-resolution 11C-(R)-PK11195 PET scans of the hands and wrists were performed. For all metacarpophalangeal, proximal interphalangeal, and wrist joints (i.e., 22 joints per patient), tracer uptake was scored semiquantitatively (0-3 scale) by 2 observers who were blinded with regard to the clinical data. Patients were followed up prospectively for 24 months to investigate the development of clinical arthritis. RESULTS: Overall agreement and kappa values for the readings of the 2 observers were, respectively, 97% and 0.91 (95% confidence interval [95% CI] 0.74-1) at the patient level and 99% and 0.81 (95% CI 0.65-0.96) at the joint level. In 4 patients, at least 1 and as many as 5 PET-positive joints (score≥1) were found at baseline. Within 2 years of followup, 9 patients had developed clinical arthritis. This included all 4 patients with positive findings on the 11C-(R)-PK11195 scan, who developed clinical arthritis in the hand/wrist region, as identified on PET scans. Of the 5 remaining arthritis patients with negative findings on PET scans, 2 developed arthritis in the hand joints and 3 developed arthritis at locations outside the field of view of the PET scanner. CONCLUSION: Subclinical arthritis in ACPA-positive arthralgia patients could be visualized by 11C-(R)-PK11195 PET scanning and was associated with development of arthritis within 2 years of followup. This indicates that 11C-(R)-PK11195 PET may be useful in determining arthritis activity in the preclinical phase of RA.

Widespread and prolonged increase in (R)-(11)C-PK11195 binding after traumatic brain injury.

UNLABELLED: Our objective was to measure (R)-(11)C-PK11195 binding as an indirect marker of neuronal damage after traumatic brain injury (TBI). METHODS: Dynamic (R)-(11)C-PK11195 PET scans were acquired for 8 patients 6 mo after TBI and for 7 age-matched healthy controls. (R)-(11)C-PK11195 binding was assessed using the simplified reference tissue model. Because of widespread traumatic changes in TBI, an anatomic reference region could not be defined. Therefore, supervised cluster analysis was used to generate an appropriate reference tissue input. RESULTS: Increased whole-brain binding of (R)-(11)C-PK11195 was observed in TBI patients. Regional analysis indicated that increased (R)-(11)C-PK11195 binding was widespread over the brain. CONCLUSION: Six months after TBI, there was a prolonged and widespread increase in (R)-(11)C-PK11195 binding, which is indicative of diffuse neuronal damage.

Measuring response to therapy using FDG PET: semi-quantitative and full kinetic analysis.

PURPOSE: Imaging with positron emission tomography (PET) using (18)F-2-fluoro-2-deoxy-D: -glucose (FDG) plays an increasingly important role for response assessment in oncology. Several methods for quantifying FDG PET results exist. The goal of this study was to analyse and compare various semi-quantitative measures for response assessment with full kinetic analysis, specifically in assessment of novel therapies. METHODS: Baseline and response dynamic FDG studies from two different longitudinal studies (study A: seven subjects with lung cancer and study B: six subjects with gastrointestinal cancer) with targeted therapies were reviewed. Quantification of tumour uptake included full kinetic methods, i.e. nonlinear regression (NLR) and Patlak analyses, and simplified measures such as the simplified kinetic method (SKM) and standardized uptake value (SUV). An image-derived input function was used for NLR and Patlak analysis. RESULTS: There were 18 and 9 lesions defined for two response monitoring studies (A and B). In all cases there was excellent correlation between Patlak- and NLR-derived response (R (2) > 0.96). Percentage changes seen with SUV were significantly different from those seen with Patlak for both studies (p < 0.05). After correcting SUV for plasma glucose, SUV and Patlak responses became similar for study A, but large differences remained for study B. Further analysis revealed that differences in responses amongst methods in study B were primarily due to changes in the arterial input functions. CONCLUSION: Use of simplified methods for assessment of drug efficacy or treatment response may provide different results than those seen with full kinetic analysis.

Day-to-day test-retest variability of CBF, CMRO2, and OEF measurements using dynamic 15O PET studies.

PURPOSE: We assessed test-retest variability of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF) measurements derived from dynamic (15)O positron emission tomography (PET) scans. PROCEDURES: In seven healthy volunteers, complete test-retest (15)O PET studies were obtained; test-retest variability and left-to-right ratios of CBF, CBV, OEF, and CMRO(2) in arterial flow territories were calculated. RESULTS: Whole-brain test-retest coefficients of variation for CBF, CBV, CMRO(2), and OEF were 8.8%, 13.8%, 5.3%, and 9.3%, respectively. Test-retest variability of CBV left-to-right ratios was <7.4% across all territories. Corresponding values for CBF, CMRO(2), and OEF were better, i.e., <4.5%, <4.0%, and <1.4%, respectively. CONCLUSIONS: The test-retest variability of CMRO(2) measurements derived from dynamic (15)O PET scans is comparable to within-session test-retest variability derived from steady-state (15)O PET scans. Excellent regional test-retest variability was observed for CBF, CMRO(2), and OEF. Variability of absolute CBF and OEF measurements is probably affected by physiological day-to-day variability of CBF.

In vivo validation of reconstruction-based resolution recovery for human brain studies.

The aim of this study was to validate in vivo the accuracy of a reconstruction-based partial volume correction (PVC), which takes into account the point spread function of the imaging system. The NEMA NU2 Image Quality phantom and five healthy volunteers (using [(11)C]flumazenil) were scanned on both HR+ and high-resolution research tomograph (HRRT) scanners. HR+ data were reconstructed using normalization and attenuation-weighted ordered subsets expectation maximization (NAW-OSEM) and a PVC algorithm (PVC-NAW-OSEM). HRRT data were reconstructed using 3D ordinary Poisson OSEM (OP-OSEM) and a PVC algorithm (PVC-OP-OSEM). For clinical studies, parametric volume of distribution (V(T)) images were generated. For phantom data, good recovery was found for both OP-OSEM (0.84 to 0.97) and PVC-OP-OSEM (0.91 to 0.98) HRRT reconstructions. In addition, for the HR+, good recovery was found for PVC-NAW-OSEM (0.84 to 0.94), corresponding well with OP-OSEM. Finally, for clinical data, good correspondence was found between PVC-NAW-OSEM and OP-OSEM-derived V(T) values (slope: 1.02+/-0.08). This study showed that HR+ image resolution using PVC-NAW-OSEM was comparable to that of the HRRT scanner. As the HRRT has a higher intrinsic resolution, this agreement validates reconstruction-based PVC as a means of improving the spatial resolution of the HR+ scanner and thereby improving the quantitative accuracy of positron emission tomography.

Reference tissue models and blood-brain barrier disruption: lessons from (R)-[11C]PK11195 in traumatic brain injury.

UNLABELLED: (R)-[(11)C]PK11195 is a tracer for activated microglia. The purpose of this study was to assess the validity of the simplified reference tissue model for analyzing (R)-[(11)C]PK11195 studies in traumatic brain injury (TBI), where blood-brain barrier disruptions are likely. METHODS: Dynamic (R)-[(11)C]PK11195 scans were acquired at 3 time points after TBI. Plasma input-derived binding potential (BP(ND)(PI)), volume of distribution (V(T)) and K(1)/k(2), and simplified reference tissue model-derived binding potential (BP(ND)(SRTM)) were obtained. Simulations were performed to assess the effect of varying K(1)/k(2). RESULTS: Early after TBI, an increase in V(T), but not in BP(ND)(PI), was found. Early K(1)/k(2) correlated with V(T) and BP(ND)(SRTM) but not with BP(ND)(PI). One and 6 mo after TBI, BP(ND)(SRTM) correlated with BP(ND)(PI). CONCLUSION: Early after TBI, (R)-[(11)C]PK11195 studies should be analyzed using plasma input models.