Single Positron Emission Tomography Scan Research Articles

Quantitative PET imaging and modeling of molecular blood-brain barrier permeability.

Blood-brain barrier (BBB) disruption is involved in the pathogenesis and progression of many neurological and systemic diseases. Non-invasive assessment of BBB permeability in humans has mainly been performed with dynamic contrast-enhanced magnetic resonance imaging, evaluating the BBB as a structural barrier. Here, we developed a novel non-invasive positron emission tomography (PET) method in humans to measure the BBB permeability of molecular radiotracers that cross the BBB through different transport mechanisms. Our method uses high-temporal resolution dynamic imaging and kinetic modeling to jointly estimate cerebral blood flow and tracer-specific BBB transport rate from a single dynamic PET scan and measure the molecular permeability-surface area (PS) product of the radiotracer. We show our method can resolve BBB PS across three PET radiotracers with greatly differing permeabilities, measure reductions in BBB PS of 18 F-fluorodeoxyglucose (FDG) in healthy aging, and demonstrate a possible brain-body association between decreased FDG BBB PS in patients with metabolic dysfunction-associated steatotic liver inflammation. Our method opens new directions to efficiently study the molecular permeability of the human BBB in vivo using the large catalogue of available molecular PET tracers.

Application of PET imaging delta radiomics for predicting progression-free survival in rare high-grade glioma

This study assesses the feasibility of using a sample-efficient model to investigate radiomics changes over time for predicting progression-free survival in rare diseases. Eighteen high-grade glioma patients underwent two L-3,4-dihydroxy-6-[18F]-fluoro-phenylalanine positron emission tomography (PET) dynamic scans: the first during treatment and the second at temozolomide chemotherapy discontinuation. Radiomics features from static/dynamic parametric images, alongside conventional features, were extracted. After excluding highly correlated features, 16 different models were trained by combining various feature selection methods and time-to-event survival algorithms. Performance was assessed using cross-validation. To evaluate model robustness, an additional dataset including 35 patients with a single PET scan at therapy discontinuation was used. Model performance was compared with a strategy extracting informative features from the set of 35 patients and applying them to the 18 patients with 2 PET scans. Delta-absolute radiomics achieved the highest performance when the pipeline was directly applied to the 18-patient subset (support vector machine (SVM) and recursive feature elimination (RFE): C-index = 0.783 [0.744–0.818]). This result remained consistent when transferring informative features from 35 patients (SVM + RFE: C-index = 0.751 [0.716–0.784], p = 0.06). In addition, it significantly outperformed delta-absolute conventional (C-index = 0.584 [0.548–0.620], p < 0.001) and single-time-point radiomics features (C-index = 0.546 [0.512–0.580], p < 0.001), highlighting the considerable potential of delta radiomics in rare cancer cohorts.

Dual-Tracer PET Image Separation by Deep Learning: A Simulation Study

Multiplexed positron emission tomography (PET) imaging provides perfectly registered simultaneous functional and molecular imaging of more than one biomarker. However, the separation of the multiplexed PET signals within a single PET scan is challenging due to the fact that all PET tracers emit positrons, which, after annihilating with a nearby electron, give rise to 511 keV photon pairs that are detected in coincidence. Compartment modelling can separate single-tracer PET signals from multiplexed signals based on the differences in bio-distribution kinetics and radioactive decay. However, the compartment-modelling-based method requires staggered injections and assumes that each tracer’s input function is known. In this paper, we propose a deep-learning-based method to simultaneously separate dual-tracer PET signals without explicitly knowing the input functions. We evaluate the proposed deep-learning-based separation method on dual-tracer [18F]FDG and [11C]MET PET simulations and compare its separation performance to that of the compartment-modelling-based method, assessing performance dependence on the time interval between tracer injections as well as on the amount of training data. It is shown that the proposed method implicitly denoises the separated images and offers reduced variance in the separated images compared to compartment modelling.

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

BackgroundQuantitative 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.ResultsIDIFs 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%.ConclusionOur 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.

13N-ammonia positron emission tomography-derived endocardial strain for the assessment of ischemia using feature-tracking in high-resolution cine imaging

BackgroundAssessing endocardial strain using a single 13N-ammonia positron emission tomography (PET) scan would be clinically useful, given the association between ischemia and myocardial deformation. However, no software has been developed for strain analysis using PET. We evaluated the clinical potential of feature tracking-derived strain values measured using PET, based on associations with the myocardial flow reserve (MFR). Methods and ResultsThis retrospective study included 95 coronary artery disease patients who underwent myocardial 13N-ammonia PET. Semi-automatic measurements were made using a feature-tracking technique during myocardial cine imaging, and values were calculated using a 16-segment model. Adenosine-stressed global circumferential strain (CS) and global longitudinal strain (LS) values were compared with global MFR values. Stressed and resting global strain values were also compared. Global strain values were significantly lower in 39 patients with abnormal MFRs [< 2.0] than in 56 patients with normal MFRs [≥ 2.0]. The global CS values in the stressed state were significantly decreased than the resting state values in patients with abnormal MFRs. ConclusionsThis study applied endocardial feature-tracking to 13N-ammonia PET, and the results suggested that blood flow and myocardial motility could be clinically assessed in ischemic patients using a single PET scan.

Three‐Dimensional Permeability Inversion Using Convolutional Neural Networks and Positron Emission Tomography

AbstractQuantification of heterogeneous multiscale permeability in geologic porous media is key for understanding and predicting flow and transport processes in the subsurface. Recent utilization of in situ imaging, specifically positron emission tomography (PET), enables the measurement of three‐dimensional (3‐D) time‐lapse radiotracer solute transport in geologic media. However, accurate and computationally efficient characterization of the permeability distribution that controls the solute transport process remains challenging. Leveraging the relationship between local permeability variation and solute advection behavior, an encoder‐decoder based convolutional neural network (CNN) is implemented as a permeability inversion scheme using a single PET scan of a radiotracer pulse injection experiment as input. The CNN can accurately capture the 3‐D spatial correlation between the permeability and the radiotracer solute arrival time difference maps in geologic cores. We first test the inversion accuracy using synthetic test datasets and then test the accuracy on a suite of experimental PET imaging datasets acquired on four different geologic cores. The network‐predicted permeability maps from the geologic cores are used to parameterize forward numerical models that are directly compared with the experimental PET imaging data. The results indicate that a single trained network can generate robust 3‐D permeability inversion maps in seconds. Numerical models parameterized with these permeability maps closely capture the experimentally observed solute arrival time behavior. This work provides an unprecedented approach for efficiently characterizing multiscale permeability heterogeneity in complex geologic samples.

Preclinical Validation of a Single-Scan Rest/Stress Imaging Technique for 13N-Ammonia Positron Emission Tomography Cardiac Perfusion Studies.

We previously proposed a technique for quantitative measurement of rest and stress absolute myocardial blood flow (MBF) using a 2-injection single-scan imaging session. Recently, we validated the method in a pig model for the long-lived radiotracer 18F-Flurpiridaz with adenosine as a pharmacological stressor. The aim of the present work is to validate our technique for 13NH3. Nine studies were performed in 6 pigs; 5 studies were done in the native state and 4 after infarction of the left anterior descending artery. Each study consisted of 3 dynamic scans: a 2-injection rest-rest single-scan acquisition (scan A), a 2-injection rest/stress single-scan acquisition (scan B), and a conventional 1-injection stress acquisition (scan C). Variable doses of adenosine combined with dobutamine were administered to induce a wide range of MBF. The 2-injection single-scan measurements were fitted with our nonstationary kinetic model (MGH2). In 4 studies, 13NH3 injections were paired with microsphere injections. MBF estimates obtained with our method were compared with those obtained with the standard method and with microspheres. We used a model-based method to generate separate rest and stress perfusion images. In the absence of stress (scan A), the MBF values estimated by MGH2 were nearly the same for the 2-radiotracer injections (mean difference: 0.067±0.070 mL·min-1·cc-1, limits of agreement: [-0.070 to 0.204] mL·min-1·cc-1), showing good repeatability. Bland-Altman analyses demonstrated very good agreement with the conventional method for both rest (mean difference: -0.034±0.035 mL·min-1·cc-1, limits of agreement: [-0.103 to 0.035] mL·min-1·cc-1) and stress (mean difference: 0.057±0.361 mL·min-1·cc-1, limits of agreement: [-0.651 to 0.765] mL·min-1·cc-1) MBF measurements. Positron emission tomography and microsphere MBF measurements correlated closely. Very good quality perfusion images were obtained. This study provides in vivo validation of our single-scan rest-stress method for 13NH3 measurements. The 13NH3 rest/stress myocardial perfusion imaging procedure can be compressed into a single positron emission tomography scan session lasting less than 15 minutes.

5th Annual Immuno-Oncology 360° Conference: Spanning Science and Business to Bring New Therapies to Patients

5th Annual Immuno-Oncology 360° Conference: Spanning Science and Business to Bring New Therapies to Patients

Intravenous ethanol increases dopamine release in the ventral striatum in humans: PET study using bolus-plus-infusion administration of [(11)C]raclopride.

Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of experimental animals, but positron emission tomography (PET) studies using the single-bolus protocol of the [(11)C]-raclopride competition paradigm have yielded conflicting results in humans. To resolve disparate previous findings, we utilized the bolus-plus-infusion (B/I) method, allowing both baseline and intervention quantification of [(11)C]raclopride binding during a single 105-minute PET scan, to investigate possible ethanol-induced DA release in nine healthy male subjects. A 25-minute intravenous ethanol (7.6%) infusion, resulting in a 1.3 g/L mean blood ethanol concentration, was administered using masked timing during the PET scan. Automated region-of-interest analysis testing the difference between baseline (40-50 minutes) and intervention (60-85 minutes) revealed an average 12.6% decrease in [(11)C]raclopride binding in the ventral striatum (VST, P=0.003) including the NAcc. In addition, a shorter time interval from the start of ethanol infusion to the first subjective effect was associated with a greater binding potential decrease bilaterally in the VST (r=0.92, P=0.004), and the feeling of pleasure was associated with a decrease in binding potential values in both the caudate nucleus (r=-0.87, P=0.003) and putamen (r=-0.74; P=0.02). These results confirm that ethanol induces rapid DA release in the limbic striatum, which can be reliably estimated using the B/I method in one imaging session.

Rapid Quantitative CBF and CMRO2 Measurements from a Single PET Scan with Sequential Administration of Dual 15O-Labeled Tracers

Positron emission tomography (PET) with 15O tracers provides essential information in patients with cerebral vascular disorders, such as cerebral blood flow (CBF), oxygen extraction fraction (OEF), and metabolic rate of oxygen (CMRO2). However, most of techniques require an additional C15O scan for compensating cerebral blood volume (CBV). We aimed to establish a technique to calculate all functional images only from a single dynamic PET scan, without losing accuracy or statistical certainties. The technique was an extension of previous dual-tracer autoradiography (DARG) approach, but based on the basis function method (DBFM), thus estimating all functional parametric images from a single session of dynamic scan acquired during the sequential administration of H215O and 15O2. Validity was tested on six monkeys by comparing global OEF by PET with those by arteriovenous blood sampling, and tested feasibility on young healthy subjects. The mean DBFM-derived global OEF was 0.57±0.06 in monkeys, in an agreement with that by the arteriovenous method (0.54±0.06). Image quality was similar and no significant differences were seen from DARG; 3.57%±6.44% and 3.84%±3.42% for CBF, and −2.79%±11.2% and −6.68%±10.5% for CMRO2. A simulation study demonstrated similar error propagation between DBFM and DARG. The DBFM method enables accurate assessment of CBF and CMRO2 without additional CBV scan within significantly shortened examination period, in clinical settings.

Measurement of Density and Affinity for Dopamine D2 Receptors by a Single Positron Emission Tomography Scan with Multiple Injections of [11C]raclopride

Positron emission tomography (PET) with [(11)C]raclopride has been used to investigate the density (B(max)) and affinity (K(d)) of dopamine D(2) receptors related to several neurological and psychiatric disorders. However, in assessing the B(max) and K(d), multiple PET scans are necessary under variable specific activities of administered [(11)C]raclopride, resulting in a long study period and unexpected physiological variations. In this paper, we have developed a method of multiple-injection graphical analysis (MI-GA) that provides the B(max) and K(d) values from a single PET scan with three sequential injections of [(11)C]raclopride, and we validated the proposed method by performing numerous simulations and PET studies on monkeys. In the simulations, the three-injection protocol was designed according to prior knowledge of the receptor kinetics, and the errors of B(max) and K(d) estimated by MI-GA were analyzed. Simulations showed that our method could support the calculation of B(max) and K(d), despite a slight overestimation compared with the true magnitudes. In monkey studies, we could calculate the B(max) and K(d) of diseased or normal striatum in a 150 mins scan with the three-injection protocol of [(11)C]raclopride. Estimated B(max) and K(d) values of D(2) receptors in normal or partially dopamine-depleted striatum were comparable to the previously reported values.

Quantitative evaluation of changes in binding potential with a simplified reference tissue model and multiple injections of [11C]raclopride

Positron emission tomography (PET) with [11C]raclopride is widely used to investigate temporal changes in the dopamine D2 receptor system attributed to the dopamine release. The simplified reference tissue model (SRTM) can be used to determine the binding potential (BPND) value using the time–activity curve (TAC) of the reference region as input function. However, in assessing temporal changes in BPND using the SRTM, multiple [11C]raclopride PET scans are required, and a second scan must be performed after the disappearance of the [11C]raclopride administered in the first scan. In this study, we have developed an extended multiple-injection SRTM to estimate the BPND change, from a single PET scan with multiple injections of [11C]raclopride, and we have validated this approach by performing numerous simulations and studies on monkeys. In the computer simulations, TACs were generated for dual injections of [11C]raclopride, in which binding conditions changed during the scans, and the BPND values before, and after, the second injection were estimated by the proposed method. As a result, the reduction in BPND was correlated, either with the integral of released dopamine, or with the administered mass of raclopride. This method was applied to studies on monkeys, and was capable of determining two identical BPND values when there were no changes in binding conditions. The BPND after the second injection decreased when binding conditions changed due to an increase in administered raclopride. An advantage of the proposed method is the shortened scan period for the quantitative assessment of the BPND change for neurotransmitter competition studies.

Separation of input function for rapid measurement of quantitative CMRO2 and CBF in a single PET scan with a dual tracer administration method

Cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF) and cerebral blood flow (CBF) images can be quantified using positron emission tomography (PET) by administrating 15O-labelled water (H152O) and oxygen (15O2). Conventionally, those images are measured with separate scans for three tracers C15O for CBV, H152O for CBF and 15O2 for CMRO2, and there are additional waiting times between the scans in order to minimize the influence of the radioactivity from the previous tracers, which results in a relatively long study period. We have proposed a dual tracer autoradiographic (DARG) approach (Kudomi et al 2005), which enabled us to measure CBF, OEF and CMRO2 rapidly by sequentially administrating H152O and 15O2 within a short time. Because quantitative CBF and CMRO2 values are sensitive to arterial input function, it is necessary to obtain accurate input function and a drawback of this approach is to require separation of the measured arterial blood time–activity curve (TAC) into pure water and oxygen input functions under the existence of residual radioactivity from the first injected tracer. For this separation, frequent manual sampling was required. The present paper describes two calculation methods: namely a linear and a model-based method, to separate the measured arterial TAC into its water and oxygen components. In order to validate these methods, we first generated a blood TAC for the DARG approach by combining the water and oxygen input functions obtained in a series of PET studies on normal human subjects. The combined data were then separated into water and oxygen components by the present methods. CBF and CMRO2 were calculated using those separated input functions and tissue TAC. The quantitative accuracy in the CBF and CMRO2 values by the DARG approach did not exceed the acceptable range, i.e., errors in those values were within 5%, when the area under the curve in the input function of the second tracer was larger than half of the first one. Bias and deviation in those values were also compatible to that of the conventional method, when noise was imposed on the arterial TAC. We concluded that the present calculation based methods could be of use for quantitatively calculating CBF and CMRO2 with the DARG approach.

Rapid Quantitative Measurement of CMRO2 and CBF by Dual Administration of 15O-Labeled Oxygen and Water During a Single PET Scan—a Validation Study and Error Analysis in Anesthetized Monkeys

Cerebral blood flow (CBF) and rate of oxygen metabolism (CMRO(2)) may be quantified using positron emission tomography (PET) with (15)O-tracers, but the conventional three-step technique requires a relatively long study period, attributed to the need for separate acquisition for each of (15)O(2), H(2)(15)O, and C(15)O tracers, which makes the multiple measurements at different physiologic conditions difficult. In this study, we present a novel, faster technique that provides a pixel-by-pixel calculation of CBF and CMRO(2) from a single PET acquisition with a sequential administration of (15)O(2) and H(2)(15)O. Experiments were performed on six anesthetized monkeys to validate this technique. The global CBF, oxygen extraction fraction (OEF), and CMRO(2) obtained by the present technique at rest were not significantly different from those obtained with three-step method. The global OEF (gOEF) also agreed with that determined by simultaneous arterio-sinus blood sampling (gOEF(A-V)) for a physiologically wide range when changing the arterial PaCO(2) (gOEF=1.03gOEF(A-V)+0.01, P<0.001). The regional values, as well as the image quality were identical between the present technique and three-step method for CBF, OEF, and CMRO(2). In addition, a simulation study showed that error sensitivity of the present technique to delay or dispersion of the input function, and the error in the partition coefficient was equivalent to that observed for three-step method. Error sensitivity to cerebral blood volume (CBV) was also identical to that in the three-step and reasonably small, suggesting that a single CBV assessment is sufficient for repeated measures of CBF/CMRO(2). These results show that this fast technique has an ability for accurate assessment of CBF/CMRO(2) and also allows multiple assessment at different physiologic conditions.

18-FDG PET scan in the staging of recurrent melanoma: additional value and therapeutic impact.

Staging of melanoma patients by means of whole body functional imaging in a single evaluation session using positron emission tomography (PET) with fluorine-18- labelled deoxy-d-glucose (FDG) as a metabolic tracer has created much interest over the last decade. After enthusiastic pilot studies, more attention has been paid to the false-negative and false-positive results of this technique than to its true therapeutic impact. This study aimed to evaluate (1) the sensitivity and specificity of this technique at a single lesion level compared with conventional screening procedures (CSP) - both of these accompanied by careful clinical examination; and (2) the additional value of the PET scan at the level of the individual patient and its therapeutic impact for different types of melanoma recurrence. A consecutive series of 100 PET scans performed on 84 melanoma patients with regional or distant recurrence according to CSP (89 PET scans) or suspicion of recurrence, i.e. inconclusive CSP (11 PET scans), were retrospectively analysed and compared with the CSP results. At the single lesion level, PET scan and CSP showed a sensitivity of 85 and 81%, a specificity of 90 and 87% and an accuracy of 88 and 84%, respectively. PET provided false-negative results for small skin metastases and brain involvement; false-positive results were associated with unrelated benign or malignant tumours and peripheral soft tissue and bone uptake. PET scan showed an additional value over and above CSP at the individual patient's level by true upstaging in 10 cases, true downstaging in 24 cases and depiction of more lesions within the same stage of disease in 15 cases. The overall therapeutic impact reached 26%: 17 out of 71 (24%) cases with regional recurrence, one out of 18 cases (5.5%) with distant metastasis and eight out of 11 cases (73%) with suspicion of recurrence where CSP remained doubtful. However, in 19 cases comparison between CSP and PET resulted in discordant findings, suggesting upstaging in one area and downstaging at another site within the same patient. In conclusion, PET scan has an additional value in the staging of recurrent melanoma, providing it is accompanied by careful clinical examination and specific brain imaging. However, in the absence of evidence of metastasis or unrelated conditions at the same site on CSP, PET spots may represent false-positive images, which would falsely upgrade a patient to an incurable state, or they may be early true-positive findings, which will become evident during close follow-up.

18F-labeled fluorouracil positron emission tomography and the prognoses of colorectal carcinoma patients with metastases to the liver treated with 5-fluorouracil

Although many factors have been investigated in connection with the prognoses of colorectal carcinoma patients with metastases to the liver, a means for evaluating response and prognosis prior to the administration of standard chemotherapy has not been available. Positron emission tomography (PET) is a noninvasive means of measuring the distribution of radiolabeled cytostatic agents in tumor regions. Prior to the administration of 5-fluorouracil chemotherapy, the authors examined 14 colorectal carcinoma patients with unresectable liver metastases using a single PET scan and 18F-labeled fluorouracil (18F-FU). Clinical response and survival time were correlated with 18F-FU uptake values (SUV) measured in liver metastases 120 minutes after tracer infusion. Trapping of 18F-FU varied even among different metastases in the same patient. The range of SUV was 0.9-4.3 (mean, 2.20). Four patients with SUV exceeding 2.8 had stable disease for longer than 12 months and survived longer than 21 months. Three patients with SUV less than 1.2 had progressive disease and survived less than 12 months. The 6 patients with partial remission or stable disease had a mean SUV of 2.96 and a mean survival of 31.6 months. Eight patients with progressive disease had a mean SUV of 1.59 and a mean survival of 14.5 months (Student's t-test, P < 0.012). In scatterplot analysis, there was a statistically significant correlation between SUV and survival time. Patients with high 18F-FU uptake values are more likely to achieve at least stabilization of disease with planned chemotherapy. 18F-FU PET may be a valuable new tool for determining, prior to 5-FU-based chemotherapy, which patients are likely to have good responses and prolonged survival.