18F-FDG PET/CT for the quantification of inflammation in large carotid artery plaques.

BACKGROUND: There is currently no consensus on the methodology for quantification of 18F-FDG uptake in inflammation in atherosclerosis. In this study, we explore different methods for quantification of 18F-FDG uptake in carotid atherosclerotic plaques and correlate the uptake values to histological assessments of inflammation. METHODS AND RESULTS: Forty-four patients with atherosclerotic stenosis ≥70% of the internal carotid artery underwent 18F-FDG PET/CT. Maximum standardized uptake values (SUVmax) from all plaque-containing slices were collected. SUVmax for the single highest and the mean of multiple slices with and without blood background correction (by subtraction (cSUV) or by division (target-to-background ratio (TBR)) were calculated. Following endarterectomy 30 plaques were assessed histologically. The length of the plaques at CT was 6-32 mm. The 18F-FDG uptake in the plaques was 1.15-2.66 for uncorrected SUVs, 1.16-3.19 for TBRs, and 0.20-1.79 for cSUVs. There were significant correlations between the different uptake values (r = 0.57-0.99, P < 0.001). Methods with and without blood background correction showed similar, moderate correlations to the amount of inflammation assessed at histology (r = 0.44-0.59, P < 0.02). CONCLUSIONS: In large stenotic carotid plaques, 18F-FDG uptake reflects the inflammatory status as assessed at histology. Increasing number of PET slices or background correction did not change the correlation.

Respiratory gated and prolonged acquisition 18F-FDG PET improve preoperative assessment of colorectal liver metastases.

BACKGROUND: Detection of small liver metastases from colorectal cancer by 18F-FDG PET/CT is hampered by high physiologic uptake in the liver parenchyma and respiratory movements during image acquisition. PURPOSE: To investigate whether two tailored 18F-FDG PET liver acquisitions (prolonged liver acquisition time [PL-PET] and repeated breath-hold respiratory gated liver acquisition [RGL-PET]) would improve detection of colorectal liver metastases, when added to a standard whole body PET (WB-PET). MATERIAL AND METHODS: Twenty consecutive patients referred to our hospital for surgical treatment of colorectal liver metastases diagnosed with contrast-enhanced CT underwent preoperative 18F-FDG PET/CT tailored for detection of liver metastases. Concordance between preoperative imaging results and true findings (histology and/or follow-up imaging) as well as changes in clinical management, based on 18F-FDG PET/CT findings, were documented. Background noise, defined as the standard deviation measured in a reference region within the normal liver parenchyma, was compared between the three 18F-FDG PET/CT protocols. RESULTS: WB-PET, PL-PET, and RGL-PET showed suspicious liver lesions in 18 out of 20 patients. Compared to WB-PET alone, the combination of PL-PET and RGL-PET showed additional lesions in the liver in seven out of the 18 patients. The combination of all three PET acquisitions changed clinical management in four patients. Two patients with negative PET results were later found to have benign liver lesions. CONCLUSION: The addition of tailored liver-specific 18F-FDG PET/CT protocols (PL-PET and RGL-PET) to a WB-PET, improved the detection of intrahepatic colorectal metastases, compared to WB-PET alone. Such add-ons can change clinical patient management of potentially resectable colorectal liver metastases.

PET-CT in the assessment of lung cancer at Rikshospitalet from 2007-2011.

BACKGROUND: PET-CT is an aid in the assessment of lung cancer for identifying operable patients. The examination is recommended for most patients with non-small cell lung cancer whom the primary assessment has indicated may have a curable disease. The aim was to assess the usefulness of PET-CT for patients assumed to be operable who underwent an examination at Rikshospitalet. MATERIAL AND METHOD: Patients admitted for lung cancer assessment are registered consecutively in the department's quality database. We analysed data for the period 2007-2011 for patients whom a primary assessment had revealed to have a potentially operable tumour. For capacity reasons, some patients underwent surgery without a prior PET-CT. RESULTS: Of 651 potentially operable patients, 533 had had a PET-CT scan of which 403 (76%) had undergone surgery. We calculated that the examination had a sensitivity of 78% (95% CI 70-86) and specificity 88% (95% CI 85-91%), positive predictive value 64% (95% CI 55-72) and negative predictive value 94% (95% CI 91-96) for spreading to mediastinal lymph nodes. Diagnostic accuracy was 86% (95% CI 83-89) with kappa agreement 0.61 (95% CI 0.53-0.69) between PET-CT and actual findings of malignant or benign mediastinal lymph nodes. INTERPRETATION: PET-CT was a useful tool for selecting potentially operable lung cancer patients at Rikshospitalet in the period 2007-2011. Provided that the population we scan with PET-CT does not change, patients with a negative PET-CT can with few exceptions be referred directly for surgery without further invasive assessment.

An implementation of time-efficient respiratory-gated PET acquisition by repeated breath-holds.

BACKGROUND: Respiratory gating in positron emission tomography (PET) is used to improve detection of small tumors in the lower lung regions and in the liver, and to obtain a better estimate of the standardized uptake value (SUV). PURPOSE: To develop a time-efficient method for acquisition of respiratory-gated PET/CT that would produce one single high quality image volume corresponding to a breath-hold state. MATERIAL AND METHODS: An instrument was developed that displayed to the patient either red or green numbers, counting down from a chosen maximum to one at a rate of one dial per second. The patient was instructed to repeatedly hold the breath in moderate inspiration when red numbers were displayed and to breathe freely during display of green numbers. PET data were acquired in list mode and trigger signals were sent to the scanner and inserted into the list file each time the color of the countdown numbers switched from green to red. Data acquired during breath-holds were used to create one single image volume. RESULTS: High quality breath-hold images were obtained from 10 min data acquisition at one bed position. Improved image quality compared to standard whole-body PET was demonstrated by a significant reduction of noise (standard deviation) in regions of normal liver tissues. CONCLUSION: The instruction to perform repeated breath-holds was well understood by patients and they cooperated satisfactorily. When the new procedure is used the duration of the data acquisition may typically be reduced by a factor of 4 compared to conventional respiratory-gated protocols where the patient breathes freely.

Dynamic FDG PET for assessing early effects of cerebral hypoxia and resuscitation in new-born pigs.

PURPOSE: Changes in cerebral glucose metabolism may be an early prognostic indicator of perinatal hypoxic-ischaemic injury. In this study dynamic ¹8F-FDG PET was used to evaluate cerebral glucose metabolism in piglets after global perinatal hypoxia and the impact of the resuscitation strategy using room air or hyperoxia. METHODS: New-born piglets (n = 16) underwent 60 min of global hypoxia followed by 30 min of resuscitation with a fraction of inspired oxygen (FiO2) of 0.21 or 1.0. Dynamic FDG PET, using a microPET system, was performed at baseline and repeated at the end of resuscitation under stabilized haemodynamic conditions. MRI at 3 T was performed for anatomic correlation. Global and regional cerebral metabolic rates of glucose (CMRgl) were assessed by Patlak analysis for the two time-points and resuscitation groups. RESULTS: Global hypoxia was found to cause an immediate decrease in cerebral glucose metabolism from a baseline level (mean ± SD) of 21.2 ± 7.9 to 12.6 ± 4.7 µmol/min/ 100 g (p <0.01). The basal ganglia, cerebellum and cortex showed the greatest decrease in CMRgl but no significant differences in global or regional CMRgl between the resuscitation groups were found. CONCLUSION: Dynamic FDG PET detected decreased cerebral glucose metabolism early after perinatal hypoxia in piglets. The decrease in CMRgl may indicate early changes of mild cerebral hypoxia-ischaemia. No significant effect of hyperoxic resuscitation on the degree of hypometabolism was found in this early phase after hypoxia. Cerebral FDG PET can provide new insights into mechanisms of perinatal hypoxic- ischaemic injury where early detection plays an important role in instituting therapy.

Clinical Applications of Somatostatin Receptor (Agonist) PET Tracers beyond Neuroendocrine Tumors.

Somatostatin receptor (SSTR) agonist tracers used in nuclear medicine scans are classically used for neuroendocrine tumor diagnosis and staging. SSTR are however, expressed more widely in a variety of cells as seen in the distribution of physiological tracer uptake during whole body scans. This provides opportunities for using these tracers for applications other than NETs and meningiomas. In this qualitative systematic review, novel diagnostics in SSTR-PET imaging are reviewed. A total of 70 studies comprised of 543 patients were qualitatively reviewed. Sarcoidosis, atherosclerosis and phosphaturic mesenchymal tumors represent the most studied applications currently with promising results. Other applications remain in progress where there are many case reports but a relative dearth of cohort studies. [18F]FDG PET provides the main comparative method in many cases but represents a well-established general PET technique that may be difficult to replace, without prospective clinical studies.

Inter-reader agreement of 18F-FDG PET/CT for the quantification of carotid artery plaque inflammation.

INTRODUCTION: A significant proportion of ischemic strokes are caused by emboli from unstable atherosclerotic carotid artery plaques. Inflammation is a key feature of plaque instability. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-(18F)-fluoro-D-glucose (18F-FDG) is a promising technique to quantify plaque inflammation, but a consensus on the methodology has not been established. High inter-reader agreement is essential if 18F-FDG PET/CT is to be used as a clinical tool for the assessment of unstable plaques and stroke risk. METHODS: We assessed the inter-reader variability of different methods for quantification of 18F-FDG uptake in 43 patients with carotid artery stenosis ≥70%. Two independent readers delineated the plaque and collected maximum standardized uptake value (SUVmax) from all axial PET slices containing the atherosclerotic plaque. RESULTS: Uptake values with and without background correction were calculated and intraclass correlation coefficients were highest for uncorrected uptake values (0.97-0.98) followed by those background corrected by subtraction (0.89-0.94) and lowest for those background corrected by division (0.74-0.79). CONCLUSION: Quantification methods without background correction have the highest inter-reader agreement for 18F-FDG PET of carotid artery plaque inflammation. The use of the single highest uptake value (max SUVmax) from the plaque will facilitate the method's clinical utility in stroke prevention.

Localized internal radiotherapy with 90Y particles embedded in a new thermosetting alginate gel: a feasibility study in pigs.

BACKGROUND: Internal radiotherapy requires the localization of the radionuclide to the site of action. A new injectable alginate gel formulation intended to undergo immediate gelation in tissues and capable of encapsulating radioactive particles containing 90Y was investigated. METHODS: The formulation was injected intramuscularly, into the bone marrow compartment of the femur and intravenously, respectively, in pigs. The distribution of radioactivity in various tissues was determined. RESULTS: Following intramuscular injection, more than 90% of the radioactivity was found at the site of injection. Following injection into bone marrow, 30-40% of the radioactivity was retained at the site of injection, but a considerable amount of radioactivity was also detected in the lungs (35-45%) and the liver (5-18%). Following intravenous injection, 80-90% of the radioactivity was found in the lungs. CONCLUSION: The present formulation appears suitable for localized radiotherapy in organs and tissues having low perfusion.

Carotid plaque inflammation assessed with (18)F-FDG PET/CT is higher in symptomatic compared with asymptomatic patients.

BACKGROUND: Carotid artery plaque inflammation is thought to be an important marker of plaque vulnerability and increased stroke risk. AIM: The main aim of this study was to assess the level of agreement between 2-deoxy-2-[(18)F] fluoro-D-glucose (18F-FDG) uptake on PET (positron emission tomography) scan in carotid plaques, with cerebrovascular symptoms, carotid plaque ultrasound echogenicity and histological assessments of plaque inflammation. METHODS: Thirty-six patients with ≥70% carotid stenosis scheduled for carotid endarterectomy underwent a Colour Duplex ultrasound, (18)F-FDG PET/CT and blood tests less than 24 h prior to surgery. Plaques were defined as symptomatic when associated with ipsilateral cerebral ischemic symptoms within 30 days prior to inclusion. Plaques were assessed histologically following endarterectomy. The level of agreement between (18)F-FDG uptake (mean SUVmax and SUVmax ), and target-to-background ratio, symptoms, plaque echolucency, and histological evidence of inflammation was assessed. RESULTS: The amount of (18)F-FDG uptake in plaques and the amount of inflammation on histological assessment were significantly correlated (r = 0·521, P = 0·003). (18)F-FDG uptake was significantly higher in symptomatic plaques with median SUVmax 1·75 (1·26-2·04) in symptomatic, and 1·43 (1·15-2·28) in asymptomatic patients (P = 0·03). (18)F-FDG uptake was also positively correlated with echolucency on Doppler ultrasound (P = 0·03). CONCLUSION: (18)F-FDG uptake on PET/CT correlated with histological assessments of inflammation and was higher in patients with symptomatic compared with asymptomatic carotid artery plaques. These results support the use of (18)F-FDG PET/CT in the detection inflammation in carotid atherosclerosis, which may be of help in the detection of vulnerable plaques.

Characterization of an asymmetric add-on collimator used with a hand-held gamma probe for radioguided surgery and sentinel node detection: a demonstration of an alternative collimation method.

OBJECTIVE: The aim of the study was to investigate a new principle for collimation of gamma probes for radioguided surgery and sentinel node detection: the use of asymmetric lateral shielding. The intension was to maintain the sensitivity in the lateral and forward directions on the unshielded side while at the same time to shield the probe against high activity sources that could mask the signal from the object to be detected. METHODS: The device was constructed to shield only against photons that come from a region in space that spans approximately 180° sideways and forwards relative to the detector. The intension of the study was to demonstrate the principle rather than to document its use in the clinic. Sensitivity profiles were derived from measurements obtained while stepwise moving the probe relatively to a point source of known activity surrounded by water. The measurements were taken in the symmetry plane of the collimator where the shielding effects were expected to be most pronounced. RESULTS: The asymmetric collimator led to nearly unchanged sensitivity in the lateral and forward directions. At the same time, the field of view was effectively shrunk on the shielded side. Contributions from sources lateral and close to the shield were reduced by factors up to 45. CONCLUSION: By rotating the probe around its longitudinal axis, an asymmetric add-on shield collimator could potentially make it easier to detect a sentinel node when this is located close to a neighbouring high activity region like the urinary bladder or the injection site.

Sentinel node procedure in low-stage/low-grade penile carcinomas.

OBJECTIVE: To optimize the indication for sentinel lymph node (SLN) biopsy according to tumour size in penile carcinoma. MATERIAL AND METHODS: This was a retrospective analysis of 23 consecutive patients (median age 65 years; range 49-85 years) with primary penile carcinoma classified according to the TNM classification as stage T1-T3 who were identified as having SLNs in the groins. SLNs were detected by means of preoperative injection of a 99mTc nanocolloid around the tumour and peroperative use of a gamma detector probe. The average tumour size was 2.9+/-1.3 cm. RESULTS: In 7/25 patients with penile carcinoma examined with the SLN method, metastases to inguinal lymph nodes could be demonstrated. Two out of three patients with primary penile carcinomas classified as T1 according to the TNM classification and tumours > 3 cm in diameter had inguinal lymph node metastases. One of the patients had a micrometastasis, which was detected by means of immunohistochemical analysis. Seven out of eight patients with penile carcinomas > 3 cm in diameter had lymph node metastases. We did not observe any major surgical complications associated with the SLN procedure. CONCLUSION: These data indicate that penile carcinomas with a diameter of >3 cm should be investigated with SLN biopsy regardless of stage. However, multicentre studies are needed in order to obtain the appropriate number of patients.