Image-derived input functions from dynamic O-15-water PET scans using penalised reconstruction

BACKGROUND: Quantitative positron emission tomography (PET) scans of the brain typically require arterial blood sampling but this is complicated and logistically challenging. One solution to remove the need for arterial blood sampling is the use of image-derived input functions (IDIFs). Obtaining accurate IDIFs, however, has proved to be challenging, mainly due to the limited resolution of PET. Here, we employ penalised reconstruction alongside iterative thresholding methods and simple partial volume correction methods to produce IDIFs from a single PET scan, and subsequently, compare these to blood-sampled input curves (BSIFs) as ground truth. Retrospectively we used data from sixteen subjects with two dynamic 15O-labelled water PET scans and continuous arterial blood sampling: one baseline scan and another post-administration of acetazolamide. RESULTS: IDIFs and BSIFs agreed well in terms of the area under the curve of input curves when comparing peaks, tails and peak-to-tail ratios with R2 values of 0.95, 0.70 and 0.76, respectively. Grey matter cerebral blood flow (CBF) values showed good agreement with an average difference between the BSIF and IDIF CBF values of 2% ± and a coefficient of variation (CoV) of 7.3%. CONCLUSION: Our results show promising results that a robust IDIF can be produced for dynamic 15O–water PET scans using only the dynamic PET scan images with no need for a corresponding MRI or complex analytical techniques and thereby making routine clinical use of quantitative CBF measurements with 15O–water feasible

Arousal modulation of memory and amygdala‐parahippocampal connectivity: A PET‐psychophysiology study in specific phobia

Phobic fear is accompanied by intense bodily responses modulated by the amygdala. An amygdala moderated psychophysiological measure related to arousal is electrodermal activity. We evaluated the contributions of electrodermal activity to amygdala‐parahippocampal regional cerebral blood flow (rCBF) during phobic memory encoding in subjects with spider or snake phobia. Recognition memory was increased for phobia‐related slides and covaried with rCBF in the amygdala and the parahippocampal gyrus. The covariation between parahippocampal rCBF and recognition was related to electrodermal activity suggesting that parahippocampal memory processes were associated with sympathetic activity. Electrodermal activity further mediated the amygdala effect on parahippocampal activity. Memory encoding during phobic fear therefore seems contingent on amygdala's influence on arousal and parahippocampal activity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86974/1/j.1469-8986.2011.01231.x.pd

Elevated [11C]-D-Deprenyl Uptake in Chronic Whiplash Associated Disorder Suggests Persistent Musculoskeletal Inflammation

There are few diagnostic tools for chronic musculoskeletal pain as structural imaging methods seldom reveal pathological alterations. This is especially true for Whiplash Associated Disorder, for which physical signs of persistent injuries to the neck have yet to be established. Here, we sought to visualize inflammatory processes in the neck region by means Positron Emission Tomography using the tracer 11C-D-deprenyl, a potential marker for inflammation. Twenty-two patients with enduring pain after a rear impact car accident (Whiplash Associated Disorder grade II) and 14 healthy controls were investigated. Patients displayed significantly elevated tracer uptake in the neck, particularly in regions around the spineous process of the second cervical vertebra. This suggests that whiplash patients have signs of local persistent peripheral tissue inflammation, which may potentially serve as a diagnostic biomarker. The present investigation demonstrates that painful processes in the periphery can be objectively visualized and quantified with PET and that 11C-D-deprenyl is a promising tracer for these purposes

Comparison of quantitative [11C]PE2I brain PET studies between an integrated PET/MR and a stand-alone PET system

PET/MR systems demanded great efforts for accurate attenuation correction (AC) but differences in technology, geometry and hardware attenuation may also affect quantitative results. Dedicated PET systems using transmission-based AC are regarded as the gold standard for quantitative brain PET. The study aim was to investigate the agreement between quantitative PET outcomes from a PET/MR scanner against a stand-alone PET system.Nine patients with Parkinsonism underwent two 80-min dynamic PET scans with the dopamine transporter ligand [11C]PE2I. Images were reconstructed with resolution-matched settings using 68Ge-transmission (standalone PET), and zero-echo-time MR (PET/MR) scans for AC. Non-displaceable binding potential (BPND) and relative delivery (R1) were evaluated using volumes of interest and voxel-wise analysis.Correlations between systems were high (r >= 0.85) for both quantitative outcome parameters in all brain regions. Striatal BPND was significantly lower on PET/MR than on stand-alone PET (-7%). R1 was significantly overestimated in posterior cortical regions (9%) and underestimated in striatal (-9%) and limbic areas (-6%). The voxel-wise evaluation revealed that the MR-safe headphones caused a negative bias in both parametric BPND and R1 images. Additionally, a significant positive bias of R1 was found in the auditory cortex, most likely due to the acoustic background noise during MR imaging. The relative bias of the quantitative [11C]PE2I PET data acquired from a SIGNA PET/MR system was in the same order as the expected test-retest reproducibility of [11C]PE2I BPND and R1, compared to a stand-alone ECAT PET scanner. MR headphones and background noise are potential sources of error in functional PET/MR studies

Composite attenuation correction method using a 68Ge-transmission multi-atlas for quantitative brain PET/MR.

In positron emission tomography (PET), 68Ge-transmission scanning is considered the gold standard in attenuation correction (AC) though not available in current dual imaging systems. In this experimental study we evaluated a novel AC method for PET/magnetic resonance (MR) imaging which is essentially based on a composite database of multiple 68Ge-transmission maps and T1-weighted (T1w) MR image-pairs (composite transmission, CTR-AC). This proof-of-concept study used retrospectively a database with 125 pairs of co-registered 68Ge-AC maps and T1w MR images from anatomical normal subjects and a validation dataset comprising dynamic [11C]PE2I PET data from nine patients with Parkinsonism. CTR-AC maps were generated by non-rigid image registration of all database T1w MRI to each subject's T1w, applying the same transformation to every 68Ge-AC map, and averaging the resulting 68Ge-AC maps. [11C]PE2I PET images were reconstructed using CTR-AC and a patient-specific 68Ge-AC map as the reference standard. Standardized uptake values (SUV) and quantitative parameters of kinetic analysis were compared, i.e., relative delivery (R1) and non-displaceable binding potential (BPND). CTR-AC showed high accuracy for whole-brain SUV (mean %bias ± SD: 0.5 ± 3.5%), whole-brain R1 (-0.1 ± 3.2%), and putamen BPND (3.7 ± 8.1%). SUV and R1 precision (SD of %bias) were modest and lowest in the anterior cortex, with an R1 %bias of -1.1 ± 6.4%). The prototype CTR-AC is capable of providing accurate MRAC-maps with continuous linear attenuation coefficients though still experimental. The method's accuracy is comparable to the best MRAC methods published so far, both in SUV and as found for ZTE-AC in quantitative parameters of kinetic modelling

Image-derived input functions from dynamic 15O–water PET scans using penalised reconstruction

Background: Quantitative positron emission tomography (PET) scans of the brain typically require arterial blood sampling but this is complicated and logistically challenging. One solution to remove the need for arterial blood sampling is the use of image-derived input functions (IDIFs). Obtaining accurate IDIFs, however, has proved to be challenging, mainly due to the limited resolution of PET. Here, we employ penalised reconstruction alongside iterative thresholding methods and simple partial volume correction methods to produce IDIFs from a single PET scan, and subsequently, compare these to blood-sampled input curves (BSIFs) as ground truth. Retrospectively we used data from sixteen subjects with two dynamic 15O-labelled water PET scans and continuous arterial blood sampling: one baseline scan and another post-administration of acetazolamide. Results: IDIFs and BSIFs agreed well in terms of the area under the curve of input curves when comparing peaks, tails and peak-to-tail ratios with R2 values of 0.95, 0.70 and 0.76, respectively. Grey matter cerebral blood flow (CBF) values showed good agreement with an average difference between the BSIF and IDIF CBF values of 2% ± and a coefficient of variation (CoV) of 7.3%. Conclusion: Our results show promising results that a robust IDIF can be produced for dynamic 15O–water PET scans using only the dynamic PET scan images with no need for a corresponding MRI or complex analytical techniques and thereby making routine clinical use of quantitative CBF measurements with 15O–water feasible

Evaluation of [11C]UCB-A positron emission tomography in human brains

Background: In preclinical studies, the positron emission tomography (PET) imaging with [C-11]UCB-A provided promising results for imaging synaptic vesicle protein 2A (SV2A) as a proxy for synaptic density. This paper reports the first-in-human [C-11]UCB-A PET study to characterise its kinetics in healthy subjects and further evaluate SV2A-specific binding. Results: Twelve healthy subjects underwent 90-min baseline [C-11]UCB-A scans with PET/MRI, with two subjects participating in an additional blocking scan with the same scanning procedure after a single dose of levetiracetam (1500 mg). Our results indicated abundant [C-11]UCB-A brain uptake across all cortical regions, with slow elimination. Kinetic modelling of [C-11]UCB-A PET using various compartment models suggested that the irreversible two-tissue compartment model best describes the kinetics of the radioactive tracer. Accordingly, the Patlak graphical analysis was used to simplify the analysis. The estimated SV2A occupancy determined by the Lassen plot was around 66%. Significant specific binding at baseline and comparable binding reduction as grey matter precludes the use of centrum semiovale as reference tissue. Conclusions: [C-11]UCB-A PET imaging enables quantifying SV2A in vivo. However, its slow kinetics require a long scan duration, which is impractical with the short half-life of carbon-11. Consequently, the slow kinetics and complicated quantification methods may restrict its use in humans

PET-Scan Shows Peripherally Increased Neurokinin 1 Receptor Availability in Chronic Tennis Elbow : Visualizing Neurogenic Inflammation?

In response to pain, neurokinin 1 (NK1) receptor availability is altered in the central nervous system. The NK1 receptor and its primary agonist, substance P, also play a crucial role in peripheral tissue in response to pain, as part of neurogenic inflammation. However, little is known about alterations in NK1 receptor availability in peripheral tissue in chronic pain conditions and very few studies have been performed on human beings. Ten subjects with chronic tennis elbow were therefore examined by positron emission tomography (PET) with the NK1 specific radioligand [C-11]GR205171 before and after treatment with graded exercise. The radioligand signal intensity was higher in the affected arm as compared with the unaffected arm, measured as differences between the arms in volume of voxels and signal intensity of this volume above a reference threshold set as 2.5 SD above mean signal intensity of the unaffected arm before treatment. In the eight subjects examined after treatment, pain ratings decreased in all subjects but signal intensity decreased in five and increased in three. In conclusion, NK1 receptors may be activated, or up-regulated in the peripheral, painful tissue of a chronic pain condition. This up-regulation does, however, have moderate correlation to pain ratings. The increased NK1 receptor availability is interpreted as part of ongoing neurogenic inflammation and may have correlation to the pathogenesis of chronic tennis elbow

Evaluation of zero-echo-time attenuation correction for integrated PET/MR brain imaging-comparison to head atlas and 68Ge-transmission-based attenuation correction

Background: MRI does not offer a direct method to obtain attenuation correction maps as its predecessors (stand-alone PET and PET/CT), and bone visualisation is particularly challenging. Recently, zero-echo-time (ZTE) was suggested for MR-based attenuation correction (AC). The aim of this work was to evaluate ZTE- and atlas-AC by comparison to 68Ge-transmission scan-based AC. Nine patients underwent brain PET/MR and stand-alone PET scanning using the dopamine transporter ligand 11C-PE2I. For each of them, two AC maps were obtained from the MR images: an atlas-based, obtained from T1-weighted LAVA-FLEX imaging with cortical bone inserted using a CT-based atlas, and an AC map generated from proton-density-weighted ZTE images. Stand-alone PET 68Ge-transmission AC map was used as gold standard. PET images were reconstructed using the three AC methods and standardised uptake value (SUV) values for the striatal, limbic and cortical regions, as well as the cerebellum (VOIs) were compared. SUV ratio (SUVR) values normalised for the cerebellum were also assessed. Bias, precision and agreement were calculated; statistical significance was evaluated using Wilcoxon matched-pairs signed-rank test. Results: Both ZTE- and atlas-AC showed a similar bias of 6–8% in SUV values across the regions. Correlation coefficients with 68Ge-AC were consistently high for ZTE-AC (r 0.99 for all regions), whereas they were lower for atlas-AC, varying from 0.99 in the striatum to 0.88 in the posterior cortical regions. SUVR showed an overall bias of 2.9 and 0.5% for atlas-AC and ZTE-AC, respectively. Correlations with 68Ge-AC were higher for ZTE-AC, varying from 0.99 in the striatum to 0.96 in the limbic regions, compared to atlas-AC (0.99 striatum to 0.77 posterior cortex). Conclusions: Absolute SUV values showed less variability for ZTE-AC than for atlas-AC when compared to 68Ge-AC, but bias was similar for both methods. This bias is largely caused by higher linear attenuation coefficients in atlas- and ZTE-AC image compared to 68Ge-images. For SUVR, bias was lower when using ZTE-AC than for atlas-AC. ZTE-AC shows to be a more robust technique than atlas-AC in terms of both intra- and inter-patient variability