Nils Schramm

High-resolution SPECT using multi-pinhole collimation

The authors present a novel SPECT imaging technique for small animal research based on multipinhole collimation. This new method is an extension of single-pinhole tomography and combines high resolution with increased system sensitivity. This paper describes the multipinhole imaging system and its preliminary characterization on simulated and measured phantom data.

Efficacy of 99mTc pertechnetate and 131I radioisotope therapy in sodium/iodide symporter (NIS)-expressing neuroendocrine tumors in vivo

PurposeThere is growing interest in the human sodium/iodide symporter (NIS) gene both as a molecular imaging reporter gene and as a therapeutic gene. Here, we show the feasibility of radioisotope therapy of neuroendocrine tumors. As a separate application of NIS gene transfer, we image NIS-expressing tumors with pinhole SPECT in living subjects.MethodsBiodistribution studies and in vivo therapy experiments were performed in nude mice carrying stably NIS-expressing neuroendocrine tumor xenografts following i.v. injection of 131I and 99mTc pertechnetate. To show the usefulness of NIS as an imaging reporter gene, 99mTc pertechnetate uptake was imaged in vivo using a clinical gamma camera in combination with a custom-made single pinhole collimator, followed by SPECT/small animal MRI data coregistration.ResultsNIS-expressing neuroendocrine tumors strongly accumulated 131I and 99mTc pertechnetate, as did thyroid, stomach, and salivary gland. The volume of NIS-expressing neuroendocrine tumors decreased significantly after therapeutic administration of 131I or 99mTc pertechnetate, whereas control tumors continued to grow. NIS-mediated uptake of 99mTc pertechnetate could be imaged in vivo at high resolution with a clinical gamma camera equipped with a custom-made single pinhole collimator. High-resolution functional and morphologic information could be combined in a single three-dimensional data set by coregistration of SPECT and small animal MRI data. Lastly, we demonstrated a therapeutic effect of 99mTc pertechnetate on NIS-expressing neuroendocrine tumors in cell culture and, for the first time, in vivo, thought to be due to emitted Auger and conversion electrons.ConclusionsNIS-expressing neuroendocrine tumors efficiently concentrate radioisotopes, allowing for in vivo high-resolution small animal SPECT imaging as well as rendering possible successful radioisotope therapy of neuroendocrine tumors.

High resolution SPECT in small animal research.

Single Photon Emission Computed Tomography (SPECT) is a technique used to assess physiological and biochemical processes under in vivo conditions. SPECT generates tomographic images from blood flow, glucose metabolism and receptor characteristics using radioactively labelled substances. This paper reviews the state of the art of in vivo imaging of laboratory animals in modified human and dedicated animal SPECT scanners. SPECT cameras with special collimators currently reach spatial resolutions up to 1 mm and sensitivities of about 1000 cps/MBq, allowing observation of receptor activity concentration changes in the pico-mole range. The time resolution of such cameras strongly depends on the pharmacological behaviour of the tracer and can range from several minutes to hours. Within these limits the functional characterization of many processes is possible. SPECT also offers the possibility to set up dynamic study protocols and repeated measurements of the same animal. This technique reduces the need for sacrificing animals, as was commonly practiced before the development of animal cameras. Animal SPECT gives the opportunity to monitor physiological and biochemical processes in animals in vivo, without interfering with the system under observation, and may become a valuable adjunct to the instrumentation (autoradiography, in vitro methods) of animal research.

[123I]Iodobenzamide binding to the rat dopamine D2 receptor in competition with haloperidol and endogenous dopamine--an in vivo imaging study with a dedicated small animal SPECT.

PurposeThis study assessed [123I]iodobenzamide binding to the rat dopamine D2 receptor in competition with haloperidol and endogenous dopamine using a high-resolution small animal SPECT.MethodsSubsequent to baseline quantifications of D2 receptor binding, imaging studies were performed on the same animals after pre-treatment with haloperidol and methylphenidate, which block D2 receptors and dopamine transporters, respectively.ResultsStriatal baseline equilibrium ratios (V3″) of [123I]iodobenzamide binding were 1.42±0.31 (mean±SD). After pre-treatment with haloperidol and methylphenidate, V3″ values decreased to 0.54±0.46 (p<0.0001) and 0.98±0.48 (p=0.009), respectively.ConclusionThe decrease in [123I]iodobenzamide binding induced by pre-treatment with haloperidol reflects D2 receptor blockade, whereas the decrease in receptor binding induced by pre-treatment with methylphenidate can be interpreted in terms of competition between [123I]IBZM and endogenous dopamine. Findings show that multiple in vivo measurements of [123I]iodobenzamide binding to D2 receptors in competition with exogenous and endogenous ligands are feasible in the same animal. This may be of future relevance for the in vivo evaluation of novel radioligands as well as for studying the interrelations between pre- and/or postsynaptic radioligand binding and different levels of endogenous dopamine.

Development of a multi-pinhole detector for high-sensitivity SPECT imaging

We report on the development of a multi-pinhole detector for high-sensitivity SPECT imaging. The work is based on a high resolution SPECT system which already is in successful operation since a couple of months. The goal of the present work is to increase the sensitivity of the current detector by a factor of 30 to 40 and to optimize it for I-123 tracer development and evaluation. Besides improvements in the detector and aperture physics a multi-pinhole arrangement is envisaged. A series of Monte-Carlo simulations and preliminary phantom studies have shown the feasibility of this approach although a number of careful optimizations concerning the layout of the aperture geometry and the iterative reconstruction algorithm are still required. Results of the simulations and tests with simulated phantom data will be presented and the quality assessment procedures will be discussed.

TierSPECT: Leistungsparameter einer dedizierten Kleintier-SPECT-Kamera und erste in vivo Messungen

Zusammenfassung Die vorliegende Arbeit stellt die Leistungsparameter einer neuen Kleintierkamera (TierSPECT) vor, konstruiert zur In-vivo-Messung von Labortieren mit radioaktiv markierten Substanzen. Die Kamera besitzt im Streumedium eine tomographische Ortsauflosung von 2,7 mm und eine Sensitivitat von 22 cps/MBq in einem nutzbaren Messfeld von 82 mm im Durchmesser. Die planare Homogenitat betragt 3,3%, die tomographische abstandsabhangig zwischen 3,2% und 3,5%. Die Abweichungen zwischen eingefullter und gemessener Aktivitatskonzentration in einem zylindrischen 4-Kammer-Phantom waren geringer als 2,6%. Mittels eines neuartigen Rattenkopfphantoms mit Kammervolumina in der Grosenordnung der Ortsauflosung (zwischen 0,065 ml und 0,19 ml) konnte demonstriert werden, dass mit dem TierSPECT unter Beachtung physiologischer Randbedingungen Studien am neostriatalen dopaminergen System der Ratte moglich sind. In-vivo-Studien mit [ 99m Tc]diphosphonato-1,2-propandicarbonsaure ( 99m Tc-DPD) und [ 123 I]N-ω-fluorpropyl-2β-carbomethoxy-3β-(4-iodphenyl)-nortropan ( 123 I-FP-CIT) zeigten, dass Knochenstoffwechsel und Dopamintransporterbindung mit dem TierSPECT visualisiert werden konnen. Dabei ermoglichte die Fusion von 99m Tc-DPD- und 123 I-FP-CIT-Bildern die eindeutige Differenzierung zwischen intra- und extrazerebralen Strukturen. Nach Gabe von Methylphenidat war eine deutliche Blockade des Dopamintransporters feststellbar.

Performance of a multi-pinhole animal SPECT

We present imaging results of a high-resolution small animal SPECT. The system is based on a commercial gamma camera and a dedicated multi-pinhole collimator. This multi-pinhole imager provides a reconstructed resolution of 1.5 to 1.7 mm and a system sensitivity of up to 1000cps/MBq.

Molecular gastrin receptor localisation in mice using high-resolution SPET-MRI image fusion

The images demonstrate the biodistribution of 99mTcDemogastrin (99mTc-minigastrin) studied with a high-resolution SPET camera in a mouse bearing an AR4-2J subcutaneous tumour (rat exocrine pancreatic cancer expressing gastrin receptors). SPET sections were matched and fused with high-resolution (300 μm isotropic resolution) MR images of the same animal. Uptake of the 99mTc-Demogastrin can be seen in the renal cortex (A), the receptor-positive tumour (B), the stomach (organ with the highest physiological receptor expression (C)) and, to a very small extent, in the liver. The uptake in the tumour correlates with the MR signal of the double echo in the steady state (DESS) sequence. Intermediate MR signal areas, indicating vital tumour tissue, show high gastrin uptake. Areas of higher MR signal intensity, indicating oedema and/or necrosis, show lower 99mTc-Demogastrin uptake.

On the development of a high-resolution multi-pinhole SPECT/CT

Multi-Pinhole SPECT systems provide high-resolution and high-sensitivity imaging for small animal research. We currently perform SPECT imaging using commercial gamma cameras upgraded with multi-pinhole collimators. We have shown that for most tasks we are capable of achieving reconstructed spatial resolutions as low as 1.2 mm with average sensitivities up to 1600 cps/MBq. In an attempt to achieve better orientation in SPECT images we are equipping a compact commercial gamma camera with an X-ray CT system to create an integrated dual modality system. We are adding the CT system to our gantry to enhance the imaging capabilities of our SPECT system. Our gantry is equipped with a 3D translation stage that enables us to image objects that extend beyond the field of view in the axial direction by performing helical scan orbits. We are capable of performing such helical scan orbits for both modalities. We have designed a cost-effective CT add-on that provides additional anatomical information to the systems users. Specifically, the CT reconstructions aid in the acquisition and interpretation of the corresponding SPECT images.

On the performance of two multi-pinhole SPECT systems for small animal research

Molecular imaging calls for imaging systems with both high resolution and high sensitivity. In small-animal SPECT high resolution is typically achieved using pinhole collimation. In order to improve the sensitivity of single-pinhole systems we employ a novel collimation approach called multi-pinhole imaging. This imaging technique extends conventional single-pinhole collimation through the addition of pinholes on each collimator. An important feature of multi-pinhole imaging is the overlap of projections on the detector. This overlap results in a more efficient coverage of the detector and thus a considerable increase in sensitivity. In this contribution we report on the performance of two multi-pinhole imaging systems: a dual-headed Siemens ECAM and a triple-headed Trionix TRIAD. The big-headed ECAM being upgraded with two 10-pinhole collimators, while the medium-sized detectors of the TRIAD were equipped with three 7-pinhole apertures. Image reconstruction is performed using a dedicated OSEM algorithm. Both systems are characterized by a series of phantom measurements and tested on numerous animal studies. We will show that both systems yield excellent image quality with a reconstructed resolution of 1.2 mm and a sensitivity of up to 1600 cps/MBq. In addition to regular semi-quantitative single-isotope studies, we will present data on dual-isotope imaging, absolute tracer quantification and the fusion of the SPECT images with MR data of the same animal