Roland Chisin

Gamma camera-mounted anatomical X-ray tomography: technology, system characteristics and first images

Abstract.Scintigraphic diagnosis, based on functional image interpretation, becomes more accurate and meaningful when supported by corresponding anatomical data. In order to produce anatomical images that are inherently registered with images of emission computerised tomography acquired with a gamma camera, an X-ray transmission system was mounted on the slip-ring gantry of a GEMS Millennium VG gamma camera. The X-ray imaging system is composed of an X-ray tube and a set of detectors located on opposite sides of the gantry rotor that moves around the patient along with the nuclear detectors. A cross-sectional anatomical transmission map is acquired as the system rotates around the patient in a manner similar to a third-generation computerised tomography (CT) system. Following transmission, single-photon emission tomography (SPET) or positron emission tomography (PET) coincidence detection images are acquired and the resultant emission images are thus inherently registered to the anatomical maps. Attenuation correction of the emission images is performed with the same anatomical maps to generate transmission maps. Phantom experiments of system performance and examples of first SPET and coincidence detection patient images are presented. Despite limitations of the system when compared with a state of the art CT scanner, the transmission anatomical maps allow for precise anatomical localisation and for attenuation correction of the emission images.

Functional connectivity of the prefrontal cortex and the amygdala in posttraumatic stress disorder

BACKGROUND Persistent, intrusive re-experiencing in posttraumatic stress disorder (PTSD) is commonly construed as a failure of cingulate inhibition (i.e., extinction) over a hyperresponsive amygdala, based primarily on animal research of fear conditioning and the finding of cingulate hypoperfusion in PTSD. METHODS We examined functional connectivity in patients with PTSD and healthy trauma survivors during repeated symptom provocation using H(2)O(15) positron emission tomography. RESULTS Memory retrieval networks (right prefrontal cortex, hippocampus, and visual cortex) were common to both groups. Networks supporting autonomic and emotional control and preparatory motor action (amygdala, anterior cingulate, subcallosal gyrus, and premotor cortex) differed between the two groups and became progressively disparate with successive presentations of the traumatic script. Patterns of effective connectivity demonstrated the predominance of direct influences of the amygdala on visual cortex, subcallosal gyrus, and anterior cingulate in PTSD but not in control subjects. There was little evidence for failure of inhibition of cingulate or subcallosal cortex over the amygdala. CONCLUSIONS These patterns might represent excessive influences of the amygdala over regions involved in autonomic, and higher-order visual memory processing in PTSD. The present data suggest that inferences of direct correspondence between animal studies and pathophysiology of PTSD should be made with caution.

SPECT/CT hybrid imaging with 111In-pentetreotide in assessment of neuroendocrine tumours.

objective  Somatostatin receptor scintigraphy (SRS) of neuroendocrine (NE) tumours is often challenging because of minute lesion size and poor anatomic delineation. This study evaluates the impact of sequentially performed single‐photon emission computed tomography (SPECT)/CT fusion on SRS study interpretation and clinical management of these tumours.

CLINICAL STUDIES OF LIPOSOME-ENCAPSULATED DOXORUBICIN

Initial clinical studies with doxorubicin entrapped in the bilayer of phosphatidylglycerol-rich liposomes were hindered by the avid reticuloendothelial system (RES) uptake and by drug leakage from circulating liposomes. In contrast, recent tests of a doxorubicin formulation of polyethyleneglycol-coated liposomes (Doxil) in cancer patients indicate that the drug pharmacokinetic properties are significantly altered, with a prolonged distribution half-life of approximately 2 days. Plasma fractionation studies show that nearly all the drug measured in plasma is in liposome-encapsulated form. The dose of Doxil has been escalated from 25 to 60 mg/m2. Stomatitis is the most significant toxicity, and skin toxicity, in the form of hand-foot syndrome, may complicate the repeated administration of Doxil. A number of objective antitumor responses in a variety of malignancies have been observed, indicating that Doxil is an active antitumor compound. Polyethyleneglycol-coated liposomes show a distinct advantage over previous liposome formulations directed at the RES and appear to be a promising drug delivery system for doxorubicin.

Technetium-99m-MIBI SPECT/CT in Primary Hyperparathyroidism

The novel trend toward focused parathyroidectomy requires precise preoperative localization of the parathyroid adenoma in patients with primary hyperparathyroidism (PHPT). The present study evaluated the impact of hybrid single photon emission computed tomography/computed tomography (SPECT/CT), using 99mTc-sestamibi (MIBI), on the surgical management of these patients. In a retrospective study of 36 patients with PHPT, SPECT/CT was undertaken when planar 99mTc-MIBI scintigraphy was negative or when an ill-defined focus in the neck or an ectopic site on planar views was visualized. Imaging data were compared with intraoperative findings, and the incremental value of SPECT/CT to lesion localization and surgical procedure was assessed. Three patients with both negative planar and SPECT/CT studies subsequently underwent bilateral neck exploration, with multiglandular hyperplasia diagnosed in two patients and a parathyroid adenoma in one. Of 33 patients with a positive MIBI study, parathyroid adenoma was confined to the neck in 23 patients and to the lower neck-mediastinum in 10. SPECT/CT facilitated the surgical exploration of all 10 ectopic parathyroid adenomas and 4 of 23 cervical parathyroid adenomas, the latter four either at reexploration or in patients with nonvisualization of the thyroid after thyroidectomy. SPECT/CT contributed to the localization of parathyroid adenomas in patients with PHPT and to planning the surgical exploration in 14 of 36 (39%) patients, predominantly those with ectopic parathyroid adenomas or who had distorted neck anatomy.

Resting regional cerebral perfusion in recent posttraumatic stress disorder

BACKGROUND Brain imaging research in posttraumatic stress disorder has been largely performed on patients with chronic disease, often heavily medicated, with current or past alcohol and substance abuse. Additionally, virtually only activation brain imaging paradigms have been done in posttraumatic stress disorder, whereas in other mental disorders both resting and activation studies have been performed. METHODS Twenty-eight (11 posttraumatic stress disorder) trauma survivors underwent resting state hexamethylpropyleneamineoxime single photon emission computed tomography and magnetic resonance imaging 6 months after trauma. Eleven nontraumatized subjects served as healthy controls. RESULTS Regional cerebral blood flow in the cerebellum was higher in posttraumatic stress disorder than in both control groups. Regional cerebral blood flow in right precentral, superior temporal, and fusiform gyri in posttraumatic stress disorder was higher than in healthy controls. Cerebellar and extrastriate regional cerebral blood flow were positively correlated with continuous measures of depression and posttraumatic stress disorder. Cortisol level in posttraumatic stress disorder was negatively correlated with medial temporal lobe perfusion. Anterior cingulate perfusion and cortisol level were positively correlated in posttraumatic stress disorder and negatively correlated in trauma survivors without posttraumatic stress disorder. CONCLUSIONS Recent posttraumatic stress disorder is accompanied by elevated regional cerebral blood flow, particularly in the cerebellum. This warrants attention because the cerebellum is often used as a reference region in regional cerebral blood flow studies. The inverse correlation between plasma cortisol and medial temporal lobe perfusion may herald hippocampal damage.

Added Value of SPECT/CT for Correlation of MIBG Scintigraphy and Diagnostic CT in Neuroblastoma and Pheochromocytoma

OBJECTIVE In pheochromocytoma and neuroblastoma, pathologic findings on metaiodobenzylguanidine (MIBG) scintigraphy (planar and SPECT) and on diagnostic CT are sometimes difficult to correlate. Furthermore, CT reading may be impaired by anatomic distortion after surgery or irradiation and if contrast agent is not injected. The present study evaluates the impact of SPECT/CT fusion images on correlation and image analysis of both techniques. MATERIALS AND METHODS Eleven patients, three adults (age range, 27-64 years) with pheochromocytoma and eight children (age range, 16-72 months) with neuroblastoma, underwent 15 (123)I-MIBG scintigraphy (whole body and SPECT/CT) and diagnostic CT during follow-up after treatment, with a time interval of 2 to 30 days (mean, 12 days) between MIBG scintigraphy and diagnostic CT. The diagnostic CT scans were read twice: blindly and with knowledge of the SPECT/CT findings. The scintigraphic and anatomic data were subsequently compared and were verified by clinical outcome. RESULTS Of 15 imaging studies, there were nine cases of discordance between SPECT/CT and diagnostic CT, whereas concordant findings of planar MIBG and diagnostic CT were observed in six studies. Overall, SPECT/CT provided additional information in eight of the 15 cases (53%) and in eight of nine discordant studies (89%). In one case of pheochromocytoma in which anatomy was distorted by previous surgery and contrast agent was not injected, SPECT/CT findings guided the diagnostic CT that had initially misinterpreted the right adrenal gland as the inferior vena cava. In three of 11 studies performed for neuroblastoma, SPECT/CT facilitated the diagnostic CT reading: in one study, a small paravertebral thickening was overlooked at blind CT reading and in another case, SPECT/CT localized and characterized a soft-tissue mass medial to the iliac bone, which was missed on diagnostic CT in an area of difficult differential anatomy (bowel loops and eventual involved lymph nodes). In the third case, SPECT/CT directed the diagnostic CT to the MIBG abnormality after multiple surgical procedures. In these four cases, MIBG SPECT/CT allowed for localization of the pathologic site that was difficult to visualize on diagnostic CT. In four additional neuroblastoma studies in which a residual mass was present on diagnostic CT, planar MIBG scintigraphy was negative. SPECT/CT, focused on the area of the diagnostic CT abnormality, showed no focal MIBG uptake, thus increasing the diagnostic certainty of remission. CONCLUSION In cases of equivocal diagnostic CT, SPECT/CT bridges the gap between MIBG scintigraphy and diagnostic CT, with guidance of the diagnostic CT and characterization of its findings. In this small series, MIBG SPECT/CT increased the diagnostic certainty in 89% of discordant studies.

Potential 18F-labeled biomarkers for epidermal growth factor receptor tyrosine kinase

Abstract As PET candidate tracers for EGFr-TK, five 4-(anilino)quinazoline derivatives, each fluorinated in the aniline moiety, were prepared. Each was tested in vitro for inhibition of EGFr autophosphorylation in A431 cell line. The leading compounds were then radiolabeled with 18 F and cell binding experiments, biodistribution and PET studies in A431 tumor-bearing mice were performed. Metabolic studies were carried out in a mice control group. From our results, we concluded that while in vitro experiments indicates efficacy of 4-(anilino)quinazoline compounds, kinetic factors and rapid blood clearance make them unsuitable as tracers for nuclear medicine imaging of EGFr-TK.

68Ga-DOTA-NOC PET/CT Imaging of Neuroendocrine Tumors: Comparison with 111In-DTPA-Octreotide (OctreoScan®)

PurposeRecent data have indicated that 68Ga-DOTA-NOC positron emission tomography/X-ray computed tomography (PET/CT) may yield improved images in a shorter acquisition protocol than 111In-DTPA-octreotide (OctreoScan®, OCT). Therefore, we performed a prospective comparison of 68Ga-DOTA-NOC and OCT for the detection of neuroendocrine tumors (NETs).MethodsNineteen patients (eight carcinoid, nine pancreatic NETs, and two NE carcinoma of unknown origin) with previous positive OCT scans underwent 68Ga-DOTA-NOC PET/CT and OCT single-photon emission computed tomography imaging for staging or follow-up. Findings were compared by region and verified with conventional imaging.ResultsAll images of both modalities demonstrated focal uptake, often at multiple sites. 68Ga-DOTA-NOC images were clearer than OCT images, facilitating interpretation. Similar foci were identified with both modalities in 41 regions, with additional foci on 68Ga-DOTA-NOC in 21 and on OCT in 15 regions. CT, magnetic resonance imaging, or ultrasound confirmed the concordant findings in 31 of 41 regions and findings seen with 68Ga-DOTA-NOC only in 15 of 21 regions. Findings seen with OCT only were less clear and were only confirmed in 4 of 15 regions. 68Ga-DOTA-NOC had impact on staging in four patients and on management in three patients.ConclusionsAlthough 68Ga-DOTA-NOC and OCT images were similar, in this study, 68Ga-DOTA-NOC demonstrated more true positive tumor foci and was better tolerated by patients. This direct comparison supports replacement of OCT with 68Ga-DOTA-NOC-PET/CT in the evaluation of NETs.

Preoperative localization of parathyroid adenoma in patients with concomitant thyroid nodular disease

We have previously demonstrated the role of high-resolution ultrasonography (US) in preoperative localization of parathyroid adenoma in patients with primary hyperparathyroidism (PHPT) and no thyroid abnormalities. The present study prospectively evaluated the possible additional value of 99mTc-sestamibi (MIBI) in patients with PHPT and concomitant multinodular thyroid disease (MND). Patients with PHPT underwent US and MIBI scintigraphy prior to neck exploration. Imaging data were correlated with the site and pathology of the parathyroid tissue removed and were analyzed separately for patients with MND and those with a normal thyroid gland. Among 77 patients with a solitary parathyroid adenoma at surgery, 40 had concomitant MND, whereas 37 patients had no morphologic changes in the thyroid gland, on US or at surgery. Prior to surgery, MIBI scintigraphy depicted 58 of the 77 adenomas (75%) and US localized 51 (66%); the combined sensitivity was 87% (67/77). Among the 37 patients with no thyroid nodules, MIBI located 29 (78%) and US identified 30 (81%) of the adenomas; the combined sensitivity was 89%. In the 40 patients with MND, MIBI identified 29 adenomas (73%) and US localized only 53% (21/40); the combined sensitivity was 85%. Overall, the positive predictive value (PPV) of MIBI for detecting a solitary parathyroid adenoma was 94%, for US it was 88%, and with the two tests combined it was 97%. In patients with no thyroid abnormalities, the PPV of MIBI and US was 97%, but it decreased to 91% and 78%, respectively, in patients with MND. Two patients with false-positive findings on both MIBI and US had associated thyroid disease. Hence MIBI scintigraphy contributes to localization of a solitary parathyroid adenoma mainly in patients with concomitant MND. The combined MIBI and US modalities result in sparing these patients bilateral neck exploration.