Alejandro Sánchez-Crespo

Positron flight in human tissues and its influence on PET image spatial resolution

The influence of the positron distance of flight in various human tissues on the spatial resolution in positron emission tomography (PET) was assessed for positrons from carbon-11, nitrogen-13, oxygen-15, fluorine-18, gallium-68 and rubidium-82. The investigation was performed using the Monte Carlo code PENELOPE to simulate the transport of positrons within human compact bone, adipose, soft and lung tissue. The simulations yielded 3D distributions of annihilation origins that were projected on the image plane in order to assess their impact on PET spatial resolution. The distributions obtained were cusp-shaped with long tails rather than Gaussian shaped, thus making conventional full width at half maximum (FWHM) measures uncertain. The full width at 20% of the maximum amplitude (FW20M) of the annihilation distributions yielded more appropriate values for root mean square addition of spatial resolution loss components. Large differences in spatial resolution losses due to the positron flight in various human tissues were found for the selected radionuclides. The contribution to image blur was found to be up to three times larger in lung tissue than in soft tissue or fat and five times larger than in bone tissue. For 18F, the spatial resolution losses were 0.54xa0mm in soft tissue and 1.52xa0mm in lung tissue, compared with 4.10 and 10.5xa0mm, respectively, for 82Rb. With lung tissue as a possible exception, the image blur due to the positron flight in all human tissues has a minor impact as long as PET cameras with a spatial resolution of 5–7xa0mm are used in combination with 18F-labelled radiopharmaceuticals. However, when ultra-high spatial resolution PET cameras, with 3–4xa0mm spatial resolution, are applied, especially in combination with other radionuclides, the positron flight may enter as a limiting factor for the total PET spatial resolution—particularly in lung tissue.

Posture primarily affects lung tissue distribution with minor effect on blood flow and ventilation

We used quantitative single photon emission computed tomography to estimate the proportion of the observed redistribution of blood flow and ventilation that is due to lung tissue shift with a change in posture. Seven healthy volunteers were studied awake, breathing spontaneously. Regional blood flow and ventilation were marked using radiotracers that remain fixed in the lung after administration. The radiotracers were administered in prone or supine at separate occasions, at both occasions followed by imaging in both postures. Images showed greater blood flow and ventilation to regions dependent at the time of imaging, regardless of posture at radiotracer administration. The results suggest that a shift in lung parenchyma has a major influence on the imaged distributions. We conclude that a change from the supine to the prone posture primarily causes a change in the vertical distribution of lung tissue. The effect on the vertical distribution of blood flow and ventilation within the lung parenchyma is much less.

Regional lung blood flow and ventilation in upright humans studied with quantitative SPECT

We used quantitative Single Photon Emission Computed Tomography (SPECT) to study the effect of the upright posture on regional lung blood flow and ventilation. Nine (upright) plus seven (prone and supine) healthy volunteers were studied awake, breathing spontaneously. Regional blood flow and ventilation were marked in sitting upright, supine and prone postures using (113m)In-labeled macroaggregates and inhaled Technegas ((99m)Tc); both remain fixed in the lung after administration. All images were obtained while supine. In comparison with horizontal postures, both blood flow and ventilation were greater in caudal regions when upright. The redistribution was greater for blood flow than for ventilation, resulting in decreasing ventilation-to-perfusion ratios down the lung when upright. We conclude that gravity redistributes regional blood flow and ventilation in the upright posture, while the influence is much less in the supine and prone postures.

The influence of photon depth of interaction and non-collinear spread of annihilation photons on PET image spatial resolution

PurposeThe quality of PET imaging is impaired by parallax errors. These errors produce misalignment between the projected location of the true origin of the annihilation event and the line of response determined by the coincidence detection system. Parallax errors are due to the varying depths of photon interaction (DOI) within the scintillator and the non-collinear (NC) emission of the annihilation photons. The aim of this work was to address the problems associated with the DOI and the NC spread of annihilation photons and to develop a quantitative model to assess their impact on image spatial resolution losses for various commonly used scintillators and PET geometries.MethodsA theoretical model based on Monte Carlo simulations was developed to assess the relative influence of DOI and the NC spread of annihilation photons on PET spatial resolution for various scintillator materials (BGO, LSO, LuAP, GSO, NaI) and PET geometries.ResultsThe results demonstrate good agreement between simulated, experimental and published overall spatial resolution for some commercial systems, with maximum differences around 1xa0mm in both 2D and 3D mode. The DOI introduces an impairment of non-stationary spatial resolution along the radial direction, which can be very severe at peripheral positions. As an example, the radial spatial resolution loss due to DOI increased from 1.3xa0mm at the centre to 6.7xa0mm at 20xa0cm from the centre of a BGO camera with a 412-mm radius in 2D mode. Including the NC, the corresponding losses were 3.0xa0mm at the centre and 7.3xa0mm 20xa0cm from the centre.ConclusionWithout a DOI detection technique, it seems difficult to improve PET spatial resolution and increase sensitivity by reducing the detector ring radius or by extending the detector in the axial direction. Much effort is expended on the design and configuration of smaller detector elements but more effort should be devoted to the DOI complexity.

Postoperative regional distribution of pulmonary ventilation and perfusion in infants with congenital diaphragmatic hernia

BACKGROUND/PURPOSEnAdvances in management of patients with congenital diaphragmatic hernia (CDH) have improved mortality rates but with a risk of increased pulmonary morbidity. The prognosis for CDH survivors remains difficult to predict owing to the lack of adequate methods. We used single photon emission computed tomography (SPECT) to measure the regional distribution of ventilation and perfusion in CDH infants to quantify the degree of lung function impairment and relate it to neonatal clinical disease severity.nnnMETHODSnSingle photon emission computed tomography was performed in 12 CDH infants at the mean age of six months. Ventilation and perfusion were traced with 5 MBq Technegas and technetium-labelled albumin macro-aggregates, respectively. Neonatal clinical data collected during the patients stay in the pediatric intensive care unit was correlated with the SPECT data.nnnRESULTSnSingle photon emission computed tomography revealed varying degrees of ventilation-perfusion abnormalities which correlated with the presence of pulmonary artery hypertension, days on ventilator and days on extracorporeal membrane oxygenation.nnnCONCLUSIONSnThe grade of clinical disease severity in infants following CDH repair is closely related to the ventilation-perfusion abnormality as seen using SPECT. The persistence of pulmonary artery hypertension into the postoperative neonatal period appears to be an important pathophysiological factor related to ventilation-perfusion abnormalities. Single photon emission computed tomography provides valuable clinical information for patient follow-up.

Regional lung ventilation in humans during hypergravity studied with quantitative SPECT.

Recently we challenged the view that arterial desaturation during hypergravity is caused by redistribution of blood flow to dependent lung regions by demonstrating a paradoxical redistribution of blood flow towards non-dependent regions. We have now quantified regional ventilation in 10 healthy supine volunteers at normal and three times normal gravity (1G and 3G). Regional ventilation was measured with Technegas ((99m)Tc) and quantitative single photon emission computed tomography (SPECT). Hypergravity caused arterial desaturation, mean decrease 8%, p<0.05 vs. 1G. The ratio for mean ventilation per voxel for non-dependent and dependent lung regions was 0.81±0.12 during 1G and 1.63±0.35 during 3G (mean±SD), p<0.0001. Thus, regional ventilation was shifted from dependent to non-dependent regions. We suggest that arterial desaturation during hypergravity is caused by quantitatively different redistributions of blood flow and ventilation. To our knowledge, this is the first study presenting high-resolution measurements of regional ventilation in humans breathing normally during hypergravity.

99mTc-sestamibi uptake and histological malignancy grade in invasive breast carcinoma.

The aim of this study was to investigate whether there is a correlation between 99mTc-sestamibi uptake and histological malignancy grade in breast carcinoma. Such a correlation could, prior to surgery and histopathological analysis, facilitate selection of patients who need adjuvant therapy. Ninety-six patients with mammographically determined lesions and/or a palpable tumour suspected for malignancy underwent 99mTc-sestamibi scintimammography prior to surgery. The final diagnosis was determined by histopathological examination. Benign lesions, cancer in situ and tumours located medially in the breast were excluded. Fifty-three invasive cancer lesions in 53 patients were finally included in the study. Planar scintigraphic breast imaging included two prone lateral projections and one anterior supine projection taken 10xa0min after injection of 700xa0MBq 99mTc-sestamibi. Focal 99mTc-sestamibi uptake in breast lesions was used as the scintigraphic criterion of abnormality. Tumour to background ratios were calculated with partial volume compensation, and histological malignancy grading was performed according to the Elston classification. A correlation was found between 99mTc-sestamibi uptake and histological malignancy grade in invasive breast carcinomas (P≤0.037).

Hallmarks in prostate cancer imaging with Ga68-PSMA-11-PET/CT with reference to detection limits and quantitative properties

BackgroundGallium-68-labeled prostate-specific antigen positron emission tomography/computed tomography imaging (Ga68-PSMA-11-PET/CT) has emerged as a potential gold standard for prostate cancer (PCa) diagnosis. However, the imaging limitations of this technique at the early state of PCa recurrence/metastatic spread are still not well characterized. The aim of this study was to determine the quantitative properties and the fundamental imaging limits of Ga68-PSMA-11-PET/CT in localizing small PCa cell deposits.MethodsThe human PCa LNCaP cells (PSMA expressing) were grown and collected as single cell suspension or as 3D-spheroids at different cell numbers and incubated with Ga68-PSMA-11. Thereafter, human HCT116 cells (PSMA negative) were added to a total cell number of 2u2009×u2009105 cells per tube. The tubes were then pelleted and the supernatant aspirated. A whole-body PET/CT scanner with a clinical routine protocol was used for imaging the pellets inside of a cylindrical water phantom with increasing amounts of background activity. The actual activity bound to the cells was also measured in an automatic gamma counter. Imaging detection limits and activity recovery coefficients as a function of LNCaP cell number were obtained. The effect of Ga68-PSMA-11 mass concentration on cell binding was also investigated in samples of LnCaP cells incubated with increasing concentrations of radioligand.ResultsA total of 1u2009×u2009104 LNCaP cells mixed in a pellet of 2u2009×u2009105 cells were required to reach a 50% detection probability with Ga68-PSMA-11-PET/CT without background. With a background level of 1xa0kBq/ml, between 4u2009×u2009105 and 1u2009×u2009106 cells are required. The radioligand equilibrium dissociation constant was 27.05xa0nM, indicating high binding affinity. Hence, the specific activity of the radioligand has a profound effect on image quantification.ConclusionsGa68-PSMA-11-PET detects a small number of LNCaP cells even when they are mixed in a population of non-PSMA expressing cells and in the presence of background. The obtained image detection limits and characteristic quantification properties of Ga68-PSMA-11-PET/CT are essential hallmarks for the individualization of patient management. The use of the standardized uptake value for Ga68-PSMA-11-PET/CT image quantification should be precluded.

18F FDG-PET/CT evaluation of histological response after neoadjuvant treatment in patients with cancer of the esophagus or gastroesophageal junction

Background In most parts of the world, curatively intended treatment for esophageal cancer includes neoadjuvant therapy, either with chemoradiotherapy or chemotherapy alone, followed by esophagectomy. Currently 18F-FDG positron emission tomography/computed tomography (PET/CT) is used for preoperative disease staging, but is not well established in the evaluation of neoadjuvant treatment. Purpose To evaluate changes in PET parameters in relation to the histological primary tumor response in the surgical specimen in patients randomized to neoadjuvant chemoradiotherapy or chemotherapy. Material and Methods Patients were randomized between either neoadjuvant chemotherapy or chemoradiotherapy followed by esophagectomy.18F-FDG PET/CT exams were conducted at baseline and following neoadjuvant treatment. Standardized uptake ratio (SUR) values were measured in the primary tumor and compared as regards histological responders and non-responders as well as different treatment arms. Results Seventy-nine patients were enrolled and 51 were available for analysis. A significant rate of SUR reduction was observed (Pu2009=u20090.02) in the primary tumor in histological responders compared to non-responders. Changes in SUR were significantly greater in responders following chemoradiotherapy (Pu2009=u20090.02), but not following chemotherapy alone (Pu2009=u20090.49). There was no statistically significant difference in SUR in patients with a complete histological response compared to those with a subtotal response. Conclusion Our results are similar to those of previous studies and show that changes in the rate of SUR can be used reliably to differentiate histological responders from non-responders after neoadjuvant treatment with either chemoradiotherapy or chemotherapy. Limitations of current PET technology are likely to restrict the possibility of accurately ruling out limited residual disease.