Although [18F]fluoro-L-dopa [FDOPA] positron emission tomography (PET) has been used as a surrogate outcome measure in Parkinson's disease therapeutic trials, this biomarker has not been proven to reflect clinical status longitudinally. We completed a retrospective analysis of relationships between computerized sampling of motor performance, FDOPA PET, and clinical outcome scales, repeated over 4 years, in 26 Parkinson's disease (PD) patients and 11 healthy controls. Mixed effects analyses showed that movement time and tongue strength best differentiated PD from control subjects. In the treated PD cohort, motor performance measures changed gradually in contrast to a steady decline in striatal FDOPA uptake. Prolonged reaction and movement time were related to lower caudate nucleus FDOPA uptake, and abnormalities in hand fine force control were related to mean striatal FDOPA uptake. These findings provide evidence that regional loss of nigrostriatal inputs to frontostriatal networks affects specific aspects of motor function.
Fluorodopa; motor control; Parkinson's disease; positron emission tomography; ageing; Tongue/*physiopathology; Facial Muscles/*physiopathology
A previous study of the DOPA decarboxylase substrate 6-[18F]fluoro-L-DOPA (FDOPA) with positron emission tomography (PET) detected no difference of the net blood-brain transfer rate (Kinapp) between detoxified alcoholic patients and healthy controls. Instead, the study revealed an inverse correlation between Kinapp in left ventral striatum and alcohol craving scores. To resolve the influx and efflux phases of radiolabeled molecules, we independently estimated the unidirectional blood-brain FDOPA clearance rate (K) and the washout rate of [18F]fluorodopamine and its deaminated metabolites (kloss), and we also calculated the total distribution volume of decarboxylated metabolites and unmetabolized FDOPA as a steady-state index of the dopamine storage capacity (Vd) in brain. The craving scores in the 12 alcoholics correlated positively with the rate of loss (kloss) in the left ventral striatum. We conclude that craving is most pronounced in the individuals with relatively rapid dopamine turnover in the left ventral striatum. The blood-brain clearance rate (K), corrected for subsequent loss of radiolabeled molecules from brain, was completely normal throughout the brain of the alcoholics, in whom the volume of distribution (Vd) was found to be significantly lower in the left caudate nucleus. The magnitude of Vd in the left caudate head was reduced by 43% relative to the 16 controls, consistent with a 58% increase of kloss. We interpret the findings as indicating that a trait for rapid dopamine turnover in the ventral striatum subserves craving and reward-dependence, leading to an acquired state of increased dopamine turnover in the dorsal striatum of detoxified alcoholic patients.
To determine the diagnostic reliability of 18F-FDOPA, 13N-Ammonia and F18-FDG PET/CT in primary brain tumors. We evaluated the amino acid and glucose metabolism of brain tumors by using PET with 18F-FDOPA, 13N-Ammonia and F18-FDG PET/CT.
Materials and Methods:
Nine patients undergoing evaluation for brain tumors were studied. Tracer uptake was quantified by the use of standardized uptake values and the ratio of tumor uptake to normal identical area of contra lateral hemisphere (T/N). In addition, PET uptake with 18F-FDOPA was quantified by use of ratio of tumor uptake to striatum uptake (T/S). The results were correlated with the patient's clinical profile.
Both high-grade and low-grade tumors were well visualized with 18F-FDOPA. The sensitivity for identifying tumors was substantially higher with 18F-FDOPA PET than with F18-FDG and 13N-Ammonia PET as determined by simple visual inspection. The sensitivity for identifying recurrence in low grade gliomas is higher with 13N-Ammonia than with F18-FDG.
18F-FDOPA PET is more reliable than F18-FDG and 13N-Ammonia PET for evaluating brain tumors.
13N-Ammonia; F18-FDG; 18F-FDOPA; brain tumors; diagnosis; PET; sensitivity
The current study examined the use of voxel-wise changes in 18F-FDOPA and 18F-FLT PET uptake, referred to as parametric response maps (PRMs), to determine whether they were predictive of response to bevacizumab in patients with recurrent malignant gliomas. Twenty-four patients with recurrent malignant gliomas who underwent bevacizumab treatment were analyzed. Patients had MR and PET images acquired before and at 2 time points after bevacizumab treatment. PRMs were created by examining the percentage change in tracer uptake between time points in each image voxel. Voxel-wise increase in PET uptake in areas of pretreatment contrast enhancement defined by MRI stratified 3-month progression-free survival (PFS) and 6-month overall survival (OS) according to receiver-operating characteristic curve analysis. A decrease in PET tracer uptake was associated with longer PFS and OS, whereas an increase in PET uptake was associated with short PFS and OS. The volume fraction of increased 18F-FDOPA PET uptake between the 2 posttreatment time points also stratified long- and short-term PFS and OS (log-rank, P < .05); however, 18F-FLT uptake did not stratify OS. This study suggests that an increase in FDOPA or FLT PET uptake on PRMs after bevacizumab treatment may be a useful biomarker for predicting PFS and that FDOPA PET PRMs are also predictive of OS in recurrent gliomas treated with bevacizumab.
Bevacizumab; 18F-FDOPA; 18F-FLT, glioblastoma; PRMs
We evaluated the utility of L-3,4-dihydroxy-6-[18F]fluoro-phenylalanine ([18F]FDOPA) positron emission tomography (PET) as a method for assessing the severity of dopaminergic dysfunction in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats by comparing it with quantitative biochemical, immunohistochemical, and behavioral measurements.
Different doses of 6-OHDA (0, 7, 14, and 28 μg) were unilaterally injected into the right striatum of male Sprague-Dawley rats. Dopaminergic functional activity in the striatum was assessed by [18F]FDOPA-PET, measurement of striatal dopamine (DA) and DA metabolite levels, tyrosine hydroxylase (TH) immunostaining, and methamphetamine-induced rotational testing.
Accumulation of [18F]FDOPA in the bilateral striatum was observed in rats pretreated with both aromatic L-amino acid decarboxylase and catechol-O-methyltransferase (COMT) inhibitors. Unilateral intrastriatal injection of 6-OHDA produced a significant site-specific reduction in [18F]FDOPA accumulation. The topological distribution pattern of [18F]FDOPA accumulation in the ipsilateral striatum agreed well with the pattern in TH-stained corresponding sections. A significant positive relationship was found between Patlak plot Ki values and striatal levels of DA and its metabolites (r = 0.958). A significant negative correlation was found between both Ki values (r = -0.639) and levels of DA and its metabolites (r = -0.719) and the number of methamphetamine-induced rotations.
Ki values determined using [18F]FDOPA-PET correlated significantly with the severity of dopaminergic dysfunction. [18F]FDOPA-PET makes it possible to perform longitudinal evaluation of dopaminergic function in 6-OHDA-lesioned rats, which is useful in the development of new drugs and therapies for Parkinson's disease (PD).
Parkinson's disease; positron emission tomography; [18F]FDOPA; 6-OHDA; dopamine
Welding exposes workers to manganese (Mn) fumes, but it is unclear if this exposure damages dopaminergic neurons in the basal ganglia and predisposes individuals to develop parkinsonism. PET imaging with 6-[18F]fluoro-l-dopa (FDOPA) is a noninvasive measure of nigrostriatal dopaminergic neuron integrity. The purpose of this study is to determine whether welding exposure is associated with damage to nigrostriatal neurons in asymptomatic workers.
We imaged 20 asymptomatic welders exposed to Mn fumes, 20 subjects with idiopathic Parkinson disease (IPD), and 20 normal controls using FDOPA PET. All subjects were examined by a movement disorders specialist. Basal ganglia volumes of interest were identified for each subject. The specific uptake of FDOPA, Ki, was generated for each region using graphical analysis method.
Repeated measures general linear model (GLM) analysis demonstrated a strong interaction between diagnostic group and region (F4,112 = 15.36, p < 0.001). Caudate Kis were lower in asymptomatic welders (0.0098 + 0.0013 minutes−1) compared to control subjects (0.0111 + 0.0012 minutes−1, p = 0.002). The regional pattern of uptake in welders was most affected in the caudate > anterior putamen > posterior putamen. This uptake pattern was anatomically reversed from the pattern found in subjects with IPD.
Active, asymptomatic welders with Mn exposure demonstrate reduced FDOPA PET uptake indicating dysfunction in the nigrostriatal dopamine system. The caudate Ki reduction in welders may represent an early (asymptomatic) marker of Mn neurotoxicity and appears to be distinct from the pattern of dysfunction found in symptomatic IPD.
Objectives: The differential diagnosis between typical idiopathic Parkinson's disease (PD) and the striatonigral variant of multiple system atrophy (MSA-P) is often difficult because of the presence of signs and symptoms common to both forms of parkinsonism, particularly at symptom onset. This study investigated striatal and midbrain findings in MSA-P and PD patients in comparison with normal controls with the use of positron emission tomography (PET) and three dimensional magnetic resonance imaging (3D MRI) based volumetry to increase the differential diagnostic accuracy between both disease entities.
Methods: Nine patients with MSA-P, 24 patients with PD, and seven healthy controls were studied by MRI and PET with 6-[18F]-fluoro-L-dopa (FDOPA), [18F]fluoro-deoxyglucose (FDG), and 11-C-Raclopride (RACLO). Striatal and extrastriatal volumes of interest (VOI) were calculated on the basis of the individual MRI data. The PET data were transferred to the VOI datasets and subsequently analysed.
Results: MSA-P differed significantly from PD patients in terms of decreased putaminal volume, glucose metabolism, and postsynaptic D2 receptor density. The striatal FDOPA uptake was equally impaired in both conditions. Neither MRI volumetry nor PET imaging of the midbrain region further contributed to the differential diagnosis between PD and MSA-P.
Conclusions: The extent and spatial distribution of functional and morphological changes in the striatum permit the differentiation of MSA-P from PD. Both, multi-tracer PET and 3D MRI based volumetry, may be considered equivalent in the assessment of different striatal abnormality in both disease entities. In contrast, MRI and PET imaging of the midbrain does not provide a further gain in diagnostic accuracy.
Parkinson Disease (PD) is a late onset disorder with age-dependent penetrance that may confound genetic studies since affected individuals may not demonstrate clinical manifestations at the time of evaluation. The use of endophenotypes, biologic surrogates for clinical disease diagnoses, may permit more accurate classification of at-risk subjects. Positron emission tomography (PET) measurements of 6-[18F]fluorodopa ([18F]FDOPA) uptake indicate nigrostriatal neuronal integrity and may provide a useful endophenotype for PD linkage studies. We performed [18F]FDOPA PET in 11 members of a large, multi-incident Amish family with PD, 24 normals and 48 people with clinically definite idiopathic PD (PD controls). Clinical diagnoses in the Amish were clinically definite PD in four, clinically probable in one, clinically possible in five, and normal in one. Abnormal [18F]FDOPA posterior putamen uptake was defined as less than three standard deviations below the normal mean. The criteria were applied to the Amish sample to determine a PET endophenotype for each. We performed genetic simulations using SLINK to model the effect phenoconversion with the PET endophenotype had on logarithm of odds (LOD) scores. PET endophenotype confirmed the status of two clinically definite subjects. Two clinically definite Amish PD subjects had normal PETs. Two possible PD were converted to “PET definite PD”. The remainder had normal PETs. The average maximum LOD score with the pre-PET was 6.14±0.84. Simulating phenoconversion of subjects with unknown phenotypes increased the LOD score to 7.36±1.23. The [18F]FDOPA PET endophenotype permits phenoconversion in multi-incident PD families and may increase LOD score accuracy and power of an informative pedigree.
Parkinson’s disease; Positron Emission Tomography; Linkage; Endophenotype; Amish
Mutations in the PINK1 gene cause autosomal recessive familial Parkinson’s disease (PD). The gene encodes a mitochondrial protein kinase that plays an important role in maintaining mitochondrial function and integrity. However, the pathophysiological link between mutation-related bioenergetic deficits and the degenerative process in dopaminergic neurons remains to be elucidated. We performed phosphorous (31P) and proton (1H) 3-T magnetic resonance spectroscopic imaging (MRSI) in 11 members of a German family with hereditary PD due to PINK1 mutations (PARK6) compared to 23 age-matched controls. All family members had prior 18-Fluorodopa (FDOPA) positron emission tomography (PET). The striatal FDOPA uptake was correlated with quantified metabolic brain mapping in MRSI. At group level, the heterozygous PINK1 mutation carriers did not show any MRSI abnormalities relative to controls. In contrast, homozygous individuals with manifest PD had putaminal GPC, PCr, HEP and β-ATP levels well above the 2SD range of controls. Across all subjects, the FDOPA Ki values correlated positively with MI (r = 0.879, p<0.001) and inversely with β-ATP (r = −0.784, p = 0.008) and GPC concentrations (r = −0.651, p = 0.030) in the putamen. Our combined imaging data suggest that the dopaminergic deficit in this family with PD due to PINK1 mutations relates to osmolyte dysregulation, while the delivery of high energy phosphates was preserved. Our results corroborate the hypothesis that PINK1 mutations result in reduced neuronal survival, most likely due to impaired cellular stress resistance.
Whiplash associated disorders are a medicolegally controversial
condition becoming increasingly worrisome in the western world. This
study was designed to evaluate perfusion and glucose metabolism in
whiplash brain. Using Tc-99m-bicisate (ECD) single photon emission computed tomography (SPECT) and F-18-fluorodeoxyglucose (FDG) PET,
six clinically and neuropsychologically controlled patients (patient
group) with whiplash syndrome and 12 normal controls (control group)
were investigated. Standardised elliptical regions of interest (ROIs)
were determined in three adjacent transaxial slices in the frontal,
parietal, temporal, and parieto-occipital cortex, cerebellum, brain
stem, basal ganglia, and thalamus. For PET, the glucose metabolic index
(GMI; =ROI uptake/global uptake at the level of the basal ganglia) and,
for SPECT, the perfusion index (PI; =ROI/global) were calculated. In
the patient group there was significant hypometabolism and
hypoperfusion in the parieto-occipital regions (on the right (R) and
left (L) side) compared with the control group: PET data: GMI
parieto-occipital R: control 1.066 (0.081) (mean (SD)), patient 0.946 (0.065); P=0.0092, Mann Whitney. GMI parieto-occipital L: control 1.034 (0.051), patient 0.922 (0.073); p=0.0067. SPECT data: PI
parieto-occipital R: control 1.262 (0.066), patient 1.102 (0.063);
P=0.0039. PI parieto-occipital L: control 1.226 (0.095), patient 1.098 (0.075); P=0.0273. In some patients there was hypometabolism (>2 SD of control) in regions other than the parieto-occipital region. It is
hypothesised that parieto-occipital hypometabolism may be caused by
activation of nociceptive afferent nerves from the upper cervical spine.
An unknown location hampers removal of pancreatic tumours. We studied the effects of enzyme inhibitors on the uptake of 6-[18F]fluoro-l-3,4-dihydroxyphenylalanine ([18F]FDOPA) in the pancreas, aiming at improved imaging of pancreatic adenocarcinoma.
Mice bearing orthotopic BxPC3 pancreatic adenocarcinoma were injected with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) and scanned with positron emission tomography/computed tomography (PET/CT). For [18F]FDOPA studies, tumour-bearing mice and sham-operated controls were pretreated with enzyme inhibitors of aromatic amino acid decarboxylase (AADC), catechol-O-methyl transferase (COMT), monoamine oxidase A (MAO-A) or a combination of COMT and MAO-A. Mice were injected with [18F]FDOPA and scanned with PET/CT. The absolute [18F]FDOPA uptake was determined from selected tissues using a gamma counter. The intratumoural biodistribution of [18F]FDOPA was recorded by autoradiography. The main [18F]FDOPA metabolites present in the pancreata were determined with radio-high-performance liquid chromatography.
[18F]FDG uptake was high in pancreatic tumours, while [18F]FDOPA uptake was highest in the healthy pancreas and significantly lower in tumours. [18F]FDOPA uptake in the pancreas was lowest with vehicle pretreatment and highest with pretreatment with the inhibitor of AADC. When mice received COMT + MAO-A inhibitors, the uptake was high in the healthy pancreas but low in the tumour-bearing pancreas.
Combined use of [18F]FDG and [18F]FDOPA is suitable for imaging pancreatic tumours. Unequal pancreatic uptake after the employed enzyme inhibitors is due to the blockade of metabolism and therefore increased availability of [18F]FDOPA metabolites, in which uptake differs from that of [18F]FDOPA. Pretreatment with COMT + MAO-A inhibitors improved the differentiation of pancreas from the surrounding tissue and healthy pancreas from tumour. Similar advantage was not achieved using AADC enzyme inhibitor, carbidopa.
Pancreas; Adenocarcinoma; [18F]FDOPA; AADC; COMT
We have previously reported the results of a 1-y double-blind, placebo-controlled study of embryonic dopamine cell implantation for Parkinson’s disease. At the end of the blinded phase, we found a significant increase in putamen uptake on 18F-fluorodopa (18F-FDOPA) PET reflecting the viability of the grafts. Nonetheless, clinical improvement was significant only in younger (age ≤ 60 y) transplant recipients, as indicated by a reduction in Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores.
We now report long-term clinical and PET outcomes from 33 of the original trial participants who were followed for 2 y after transplantation and 15 of these subjects who were followed for 2 additional years. Longitudinal changes in UPDRS motor ratings and caudate and putamen 18F-FDOPA uptake were assessed with repeated-measures ANOVA. Relationships between these changes over time were evaluated by the analysis of within-subject correlations.
We found that UPDRS motor ratings declined over time after transplantation (P < 0.001). Clinical improvement at 1 y was relatively better for the younger transplant recipients and for men, but these age and sex differences were not evident at longer-term follow-up. Significant increases in putamen 18F-FDOPA uptake were evident at all posttransplantation time points (P < 0.001) and were not influenced by either age or sex. Posttransplantation changes in putamen PET signal and clinical outcome were significantly intercorrelated (P < 0.02) over the course of the study. Image analysis at the voxel level revealed significant bilateral increases in 18F-FDOPA uptake at 1 y (P < 0.001) in the posterior putamen engraftment sites. PET signal in this region increased further at 2 and 4 y after engraftment. Concurrently, this analysis disclosed progressive declines in radiotracer uptake in the nonengrafted caudate and ventrorostral putamen. Clinical improvement after transplantation correlated with the retention of PET signal in this region at the preoperative baseline.
These results suggest that clinical benefit and graft viability are sustained up to 4 y after transplantation. Moreover, the dependence of clinical (but not imaging) outcomes on subject age and sex at 1 y may not persist over the long term. Last, the imaging changes reliably correlate with clinical outcome over the entire posttransplantation time course.
18F-FDOPA; PET; Parkinson’s disease; transplantation; long-term outcome
Background and purpose
Breast carcinoma is the most common cancer in female patients with a propensity for recurrence and metastases. The accuracy of ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), scintimammography (SMM) and positron emission tomography (PET) in diagnosing the recurrent and/or breast cancer has never been systematically assessed, and present systematic review was aimed at this issue.
MEDLINE and EMBASE were searched for articles dealt with detection of recurrent and/or metastatic breast cancer by US, CT, MRI, SMM or PET whether interpreted with or without the use of CT. Histopathologic analysis and/or close clinical and imaging follow-up for at least 6 months were used as golden reference. We extracted data to calculate sensitivity, specificity, summary receiver operating characteristic curves and area under the curve and to test for heterogeneity.
In 42 included studies, US and MRI had highest pooled specificity (0.962 and 0.929, respectively); MRI and PET had highest pooled sensitivity (0.9500 and 0.9530, respectively). The AUC of US, CT, MRI, SMM and PET was 0.9251, 0.8596, 0.9718, 0.9386 and 0.9604, respectively. Results of pairwise comparison between each modality demonstrated that AUC of MRI and PET was higher than that of US or CT, p < 0.05. No statistical significance was found between MRI and PET. There was heterogeneity among studies and evidence of publication bias.
In conclusion, MRI seemed to be a more useful supplement to current surveillance techniques to assess patients with suspected recurrent and/or metastatic breast cancer. If MRI shows an indeterminate or benign lesion or MRI was not applicable, FDG-PET could be performed in addition.
Recurrent and/or metastatic breast cancer; US; CT; MRI; SMM; PET; Meta-analysis
To determine the diagnostic reliability of 18F-FDOPA, 13N-Ammonia and 18F-FDG PET/CT in primary brain tumors and comparison with magnetic resonance imaging (MRI).
Materials and Methods:
A total of 23 patients, 8 preoperative and 15 postoperative, undergoing evaluation for primary brain tumors were included in this study. Of them, 9/15 were operated for high grade gliomas (7/9 astrocytomas and 2/9 oligodendrogliomas) and 6/15 for low grade gliomas (5/6 astrocytomas and 1/6 oligodendroglioma). After PET study, 2 of 8 preoperative cases were histopathologically proven to be of benign etiology. 3 low grade and 2 high grade postoperative cases were disease free on 6 months follow-up. Tracer uptake was quantified by standardized uptake values (SUVmax) and the SUV max ratio of tumor to normal symmetrical area of contra lateral hemisphere (T/N). 18F-FDOPA uptake was also quantified by SUVmax ratio of tumor to striatum (T/S). Conventional MR studies were done in all patients.
Both high-grade and low-grade tumors were well visualized with 18F-FDOPA PET. Sensitivity of 18F-FDOPA PET was substantially higher (6/6 preoperative, 3/3 low grade postoperative, 7/7 high grade postoperative) than with 18F-FDG (3/6 preoperative, 1/3 low grade postoperative, 3/7 high grade postoperative) and 13N-Ammonia PET (2/6 preoperative, 1/3 low grade postoperative, 1/7 high grade postoperative). FDOPA was equally specific as FDG and Ammonia PET in operated cases but was falsely positive in two preoperative cases. Sensitivity of FDOPA (16/16) was more than MRI (13/16).
18F-FDG uptake correlates with tumor grade. Though 18F-FDOPA PET cannot distinguish between tumor grade, it is more reliable than 18F-FDG and 13N-Ammonia PET for evaluating brain tumors. 18F-FDOPA PET may prove to be superior to MRI in evaluating recurrence and residual tumor tissue. 13N-Ammonia PET did not show any encouraging results.
13N-Ammonia; 18F-FDG; 18F-FDOPA; brain tumors; MRI; PET; sensitivity
Using both a volume of interest (VOI) and whole brain voxel-wise approach, we compared rates of decline of 6-L-[18F]-fluorodopa (FDOPA) positron emission tomography (PET) uptake ipsilateral (IL) and contralateral (CL) to the initially symptomatic limbs over 4.5 years in 26 subjects with Parkinson’s disease (PD) and 11 controls. The VOI approach used six subregions: Head/body of caudate nucleus, whole putamen, and posterior putamen. The absolute rate of decline in PD was significantly greater than in controls in all subregions, but did not differ significantly by region. Ratios of uptake between regions did not change during the study with the exception of the IL putamen/caudate ratio. Both male gender and advancing age were associated with lower baseline FDOPA uptake in PD, but no difference in decline rates. In the PD group, decline rates were marginally greater during earlier time segments. Striatal FDOPA uptake was significantly correlated with disease duration and with progression of time during the study, but only moderately correlated with UPDRS scores. We conclude that FDOPA uptake in subregions of the striatum is strongly correlated with disease duration and age, and declines equally from symptom onset in PD. This implies that in idiopathic PD, relative preservation of uptake in the anterior striatum reflects a delay in pathologic involvement of nigrostriatal projections to these regions.
Parkinson’s disease; Fluorodopa positron emission tomography; disease progression; aging; gender
Noninvasive methods are needed to explore the heterogeneous tumor microenvironment and its modulation by therapy. Hybrid PET/MRI systems are being developed for small-animal and clinical use. The advantage of these integrated systems depends on their ability to provide MR images that are spatially coincident with simultaneously acquired PET images, allowing combined functional MRI and PET studies of intratissue heterogeneity. Although much effort has been devoted to developing this new technology, the issue of quantitative and spatial fidelity of PET images from hybrid PET/MRI systems to the tissues imaged has received little attention. Here, we evaluated the ability of a first-generation, small-animal MRI-compatible PET scanner to accurately depict heterogeneous patterns of radiotracer uptake in tumors.
Quantitative imaging characteristics of the MRI-compatible PET (PET/MRI) scanner were evaluated with phantoms using calibration coefficients derived from a mouse-sized linearity phantom. PET performance was compared with a commercial small-animal PET system and autoradiography in tumor-bearing mice. Pixel and structure-based similarity metrics were used to evaluate image concordance among modalities. Feasibility of simultaneous PET/MRI functional imaging of tumors was explored by following 64Cu-labeled antibody uptake in relation to diffusion MRI using cooccurrence matrix analysis.
The PET/MRI scanner showed stable and linear response. Activity concentration recovery values (measured and true activity concentration) calculated for 4-mm-diameter rods within linearity and uniform activity rod phantoms were near unity (0.97 ± 0.06 and 1.03 ± 0.03, respectively). Intratumoral uptake patterns for both 18F-FDG and a 64Cu-antibody acquired using the PET/MRI scanner and small-animal PET were highly correlated with autoradiography (r > 0.99) and with each other (r = 0.97 ± 0.01). On the basis of these data, we performed a preliminary study comparing diffusion MRI and radiolabeled antibody uptake patterns over time and visualized movement of antibodies from the vascular space into the tumor mass.
The MRI-compatible PET scanner provided tumor images that were quantitatively accurate and spatially concordant with autoradiography and the small-animal PET examination. Cooccurrence matrix approaches enabled effective analysis of multimodal image sets. These observations confirm the ability of the current simultaneous PET/MRI system to provide accurate observations of intratumoral function and serve as a benchmark for future evaluations of hybrid instrumentation.
PET/MRI; multimodal imaging; tumor heterogeneity; quantitative molecular imaging; preclinical
In this study, we aimed to assess the detection of crossed cerebellar diaschisis (CCD) following stroke by perfusion-weighted magnetic resonance imaging (PW-MRI) in comparison with positron emission tomography (PET). Both PW-MRI and 15O-water-PET were performed in acute and subacute hemispheric stroke patients. The degree of CCD was defined by regions of interest placed in the cerebellar hemispheres ipsilateral (I) and contralateral (C) to the supratentorial lesion. An asymmetry index (AI=C/I) was calculated for PET-cerebral blood flow (CBF) and MRI-based maps of CBF, cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP). The resulting AI values were compared by Bland–Altman (BA) plots and receiver operating characteristic analysis to detect the degree and presence of CCD. A total of 26 imaging procedures were performed (median age 57 years, 20/26 imaged within 48 hours after stroke). In BA plots, all four PW-MRI maps could not reliably reflect the degree of CCD. In receiver operating characteristic analysis for detection of CCD, PW-CBF performed poorly (accuracy 0.61), whereas CBV, MTT, and TTP failed (accuracy <0.60). On the basis of our findings, PW-MRI at 1.5 T is not suited to depict CCD after stroke.
crossed cerebellar diaschisis; perfusion-weighted imaging; positron emission tomography; remote inactivation; stroke
Objective: To investigate the role of 99mTc-TRODAT-1 SPECT in diagnosis and assessing severity of idiopathic Parkinson’s disease (PD). Methods: Thirty-eight patients with primary, tentative diagnosis of PD and eighteen age-matched normal controls were studied with 99mTc-TRODAT-1 SPECT imaging. The regions of interests (ROIs) were drawn manually on cerebellum (CB), occipital cortex (OC) and three transverse plane slice-views of striatums, the semiquantitative BG (background)/[(OC+CB)/2] were then calculated. Results: A lower uptake of 99mTc-TRODAT-1 in striatums were displayed in thirty-six out of thirty-eight PD patients by visual inspection, compared to controls. In twenty-four PD cases with HYS (Hoehn and Yahr scale) stage I, a greater loss of DAT uptake was found in striatum and its subregions contralateral striatum to the affected limbs than in the same regions of the controls, although the striatal uptake was bilaterally reduced. Using Spearman correlation analysis showed that the reduction of the uptake ratios significantly correlated with the UPDRS in striatum and all its subregions in the PD group (P<0.05), a similar change was also found in the putamen by using the rating scale of Hoehn and Yahr (P<0.05). However, analysis of variance (ANOVA) did not show any relationship between the decreasing uptake of 99mTc-TRODAT-1 and increasing severity of PD patients, although the specific uptake of 99mTc-TRODAT-1 was continuously decreased in the striatum by visual inspection with the progress of PD from HYS stage I to III. Conclusion: 99mTc-TRODAT-1 SPECT imaging may serve as a useful method for improving the correct diagnosis of PD. In assessing the role of 99mTc-TRODAT-1 SPECT in disease severity of PD, UPDRS can offer a comprehensive index, although the Hoehn and Yahr assessment may be available in part.
99mTc-TRODAT-1; Single photon emission computed tomography (SPECT); Parkinson’s disease (PD)
To assess quantitatively the cortical pattern profile of regional FDDNP binding to beta-amyloid and neurofibrillary tangles on MR derived cortical maps, FDDNP PET images were corrected for movement and partial volume (PV), and optimized for kernel size. 3
FDDNP DVR PET images from 23 subjects (7 with Alzheimer’s disease (AD), 6 with mild cognitive impairment and 10 controls) were obtained from Logan analysis using cerebellum as reference. A hemispheric cortical surface model for each subject was extracted from the MRI. The same transformations were applied to the FDDNP DVR PET images to map them into the same space. The cortical map with PV correction was calculated as the ratio of the DVR cortical surface and that of the simulated map, created from the mask derived from MRI and smoothed to the PET resolution. Discriminant analysis was used to order the FDDNP DVR cortical surfaces based on subjects’ disease state. Linear regression was used to assess the rate of change of DVR vs. MMSE for each hemispheric cortical surface point.
The FDDNP DVR cortical surface corrected for movement and PV had less hemispheric asymmetry. Optimal kernel size was determined to be 9mm. The corrected cortical surface map of FDDNP DVR showed clear spatial pattern that was consistent with the known pathological progression of AD.
Correcting for movement, PV as well as optimizing kernel size provide sensitive statistical analysis of FDDNP distribution which confirms in the living brain known pathology patterns earlier observed with cognitive decline with brain specimens.
cortical surface maps; MR; FDDNP PET
Changes in tumor metabolism from PET in locally advanced breast cancer (LABC) patients treated with neoadjuvant chemotherapy (NC) are predictive of pathologic response. Serial dynamic [18F]-FDG PET scans were used to compare kinetic parameters to the standardized uptake value (SUV) as predictors of pathologic response, disease-free survival (DFS) and overall survival (OS).
Seventy-five LABC patients underwent FDG PET prior to and at midpoint of NC. FDG delivery (K1), FDG flux (Ki), and SUV measures were calculated and compared by clinical and pathological tumor characteristics using regression methods and area under the receiver operating characteristic curve (AUC). Associations between K1, Ki, and SUV and DFS and OS were evaluated using the Cox proportional hazards model.
Tumors that were hormone receptor negative, high grade, highly proliferative, or of ductal histology had higher FDG Ki and SUV values; on average, FDG K1 did not differ systematically by tumor features. Predicting pathologic response in conjunction with estrogen receptor (ER) and axillary lymph node positivity, kinetic measures (AUC = 0.97) were more robust predictors compared to SUV (AUC = 0.84, P = 0.005). Changes in K1 and Ki predicted both DFS and OS, while changes in SUV predicted OS only. In multivariate modeling, only changes in K1 remained an independent prognosticator of DFS and OS.
Kinetic measures of FDG PET for LABC patients treated with NC accurately measured treatment response and predicted outcome compared to static SUV measures, suggesting kinetic analysis may hold advantage of static uptake measures for response assessment.
PET; FDG kinetics; SUV; breast cancer; neoadjuvant
We developed positron emission tomography (PET)/computed tomography (CT) viewing software (PETviewer) that can display co-registered PET and CT images obtained by PET/CT and stored on picture archiving and communication systems (PACS). PETviewer has tools for presetting windows for CT display; control bars for PET window level; zoom, pan, and pseudo-color functions; and allows the user to draw a rectangular region of interest (ROI) for standardized uptake value (SUV) measurement. SUV was calculated using PET DICOM header information and the pixel intensity in PETviewer. Reconstructed datasets of PET/CT and maximum intensity projection (MIP) of the PET images were transferred and archived in PACS. Phantom experiments were performed to evaluate the validity of image fusion. PET/CT images were displayed on an independent window in PACS. Transaxial PET images were reformatted as sagittal and coronal PET images, which were displayed with the corresponding CT and PET/CT fusion images with adjustable color and transparency. Transaxial, sagittal, and coronal PET images corresponding to the location of the cursor were shown using cine display of MIP images. All images were displayed in PETviewer within 20 s on a personal computer for PACS, which was equipped with a P4, 1.3-GHz CPU, and 512 Mb of RAM. We could measure maximum and mean SUV in a ROI using PETviewer. Transaxial fused images of patients and phantoms showed excellent registration and fusion of PET and CT images in the X and Y directions. PETviewer provided very useful clinical tools for assessing PET/CT images on PACS and should assist in maximizing the benefits derived from PET/CT imaging.
PET/CT; PACS; image fusion; multimodality imaging
The positron emission tomography (PET) tracer 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl)-nortropane (18F-FECNT) is a highly specific ligand for dopamine transporter (DAT) that yields higher peak striatum-to-cerebellum ratios and offers more favorable kinetics than most 18F-radiolabeled DAT ligands currently available. The goal of this study is to validate the use of 18F-FECNT as a PET radiotracer to assess the degree of striatal dopamine terminals denervation and midbrain dopaminergic cell loss in MPTP-treated parkinsonian monkeys. Three rhesus monkeys received weekly injections of MPTP (0.2-0.5 mg/kg) for 21 weeks, which resulted in the progressive development of a moderate level of parkinsonism. We carried out 18F-FECNT PET at baseline (twice; ten weeks apart) and at week 21 post-MPTP injections. Postmortem stereological cell counts of dopaminergic neurons in the ventral midbrain, and intensity measurements of DAT and tyrosine hydroxylase (TH) immunoreactivity in the striatum were performed and correlated with striatal and ventral midbrain PET data. Three additional monkeys were used as controls for midbrain dopaminergic cell counts, and striatal DAT or TH immunoreactivity measurements. The correlation and coefficient of variance between 18F-FECNT test-retest specific uptake ratios were 0.99 (R2) and 2.65%, respectively. The 18F-FECNT binding potential of the ventral midbrain and striatal regions was tightly correlated with postmortem stereological cell counts of nigral dopaminergic neurons (R2 = 0.91), and striatal DAT (R2 = 0.83) or TH (R2 = 0.88) immunoreactivity intensity measurements. These findings demonstrate that 18F-FECNT is a highly sensitive PET imaging ligand to quantify both striatal dopamine denervation and midbrain dopaminergic cell loss associated with parkinsonism.
Parkinson’s disease; brain imaging; transporter; dopamine; striatum; MPTP; monkey; primate; substantia nigra; midbrain; animal model
We aimed to evaluate prospectively the efficacy of positron emission tomography (PET)/computed tomography (CT) plus brain magnetic resonance imaging (MRI) for detecting extrathoracic metastases in lung adenocarcinoma. Metastatic evaluations were feasible for 442 consecutive patients (M:F=238:204; mean age, 54 yr) with a lung adenocarcinoma who underwent PET/CT (CT, without IV contrast medium injection) plus contrast-enhanced brain MRI. The presence of metastases in the brain was evaluated by assessing brain MRI or PET/CT, and in other organs by PET/CT. Diagnostic efficacies for metastasis detection with PET/CT plus brain MRI and with PET/CT only were calculated on a per-patient basis and compared from each other. Of 442 patients, 88 (20%, including 50 [11.3%] with brain metastasis) had metastasis. Regarding sensitivity of overall extrathoracic metastasis detection, a significant difference was found between PET/CT and PET/CT plus brain MRI (68% vs. 84%; P=0.03). As for brain metastasis detection sensitivity, brain MRI was significantly higher than PET/CT (88% vs. 24%; P<0.001). By adding MRI to PET/CT, brain metastases were detected in additional 32 (7% of 442 patients) patients. In lung adenocarcinoma patients, significant increase in sensitivity can be achieved for detecting extrathoracic metastases by adding dedicated brain MRI to PET/CT and thus enhancing brain metastasis detection.
PET/CT Scan; Lung Neoplasms; Neoplasm Metastasis; Brain; Magnetic Resonance Imaging; Neoplasm Staging
Many methods have been proposed for generating an image-derived input function (IDIF) exclusively from PET images. The purpose of this study was to assess the viability of a multimodality approach utilizing registered MR images. 3T-MR and HRRT-PET data were acquired from human subjects. Segmentation of both the left and right carotid arteries was performed in MR images using a 3D level sets method. Vessel centerlines were extracted by parameterization of the segmented voxel coordinates with either a single polynomial curve or a B-spline curve fitted to the segmented data. These centerlines were subsequently re-registered to static PET data to maximize the accurate classification of PET voxels in the ROI. The accuracy of this approach was assessed by comparison of the area under the curve (AUC) of the IDIF to that measured from conventional automated arterial blood sampling.
Our method produces curves similar in shape to that of blood sampling. The mean AUC ratio of the centerline region was 0.40±0.19 before re-registration and 0.69±0.26 after re-registration. Increasing the diameter of the carotid ROI produced a smooth reduction in AUC. Thus, even with the high resolution of the HRRT, partial volume correction is still necessary. This study suggests that the combination of PET information with MR segmented regions will demonstrate an improvement over regions based solely on MR or PET alone.
We recently elevated interior tomography from its origin in computed tomography (CT) to a general tomographic principle, and proved its validity for other tomographic modalities including SPECT, MRI, and others. Here we propose “omni-tomography”, a novel concept for the grand fusion of multiple tomographic modalities for simultaneous data acquisition in a region of interest (ROI). Omni-tomography can be instrumental when physiological processes under investigation are multi-dimensional, multi-scale, multi-temporal and multi-parametric. Both preclinical and clinical studies now depend on in vivo tomography, often requiring separate evaluations by different imaging modalities. Over the past decade, two approaches have been used for multimodality fusion: Software based image registration and hybrid scanners such as PET-CT, PET-MRI, and SPECT-CT among others. While there are intrinsic limitations with both approaches, the main obstacle to the seamless fusion of multiple imaging modalities has been the bulkiness of each individual imager and the conflict of their physical (especially spatial) requirements. To address this challenge, omni-tomography is now unveiled as an emerging direction for biomedical imaging and systems biomedicine.