Tumor lesion detection: when is integrated positron emission tomography/computed tomography more accurate than side-by-side interpretation of positron emission tomography and computed tomography?

OBJECTIVES: To determine if there is added value to oncology studies performed with a dedicated in-line positron emission tomography (PET)/computed tomography (CT) scanner as compared with PET read side by side with diagnostic CT (DCT). METHODS: Forty-one consecutive oncology patients referred for PET/CT who had contemporary DCT scans for review were enrolled. Body regions assessed on a DCT scan were assessed on PET/CT and by side-by-side reading of PET and DCT (SBS PET/DCT). Lesions identified on DCT, the CT portion of PET/CT, SBS PET/DCT, and the reading of fused PET/CT images were scored as benign or malignant. The PET portion of the PET/CT study was read by 2 teams: the first read the SBS PET/DCT scan and the other read the complete fused PET/CT scan. For discordant lesions, the final diagnosis was determined by pathologic findings (n = 6) or imaging follow-up (n = 21). RESULTS: Twenty-seven (16.1%) of the 168 lesions were discordant when comparing analysis of fused PET/CT and SBS PET/DCT. Sixteen (9.5%) were fundamentally discordant, and 11(6.6%) were discordant in degree of confidence. For all discordant lesions only, the sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for PET/CT were 100%, 33%, 100%, 94%, and 78%, respectively, and for SBS PET/DCT, they were 38%, 50%, 19%, 73%, and 30%, respectively (P < 0.001 for sensitivity, P = not specific for specificity). The 2 main causes for misclassification on SBS PET/DCT were incorrect localization (n = 12) and changes occurring in the time gap between DCT and PET/CT (n = 4). CONCLUSIONS: In-line PET/CT offers better lesion localization in comparison to the visual fusion of PET and CT, especially for small lymph nodes, lesions adjacent to mobile organs, or lesions adjacent to the chest or abdominal wall.     

Radiopharmaceuticals for positron emission tomography investigations of Alzheimer’s disease

Alzheimer’s disease (AD) is a common degenerative neurological disease that is an increasing medical, economical, and social problem. There is evidence that a long “asymptomatic” phase of the disease exists where functional changes in the brain are present, but structural imaging for instance with magnetic resonance imaging remains normal. Positron emission tomography (PET) is one of the tools by which it is possible to explore changes in cerebral blood flow and metabolism and the functioning of different neurotransmitter systems. More recently, investigation of protein aggregations such as amyloid deposits or neurofibrillary tangles containing tau-protein has become possible. The purpose of this paper is to review the current knowledge on various ¹⁸F- and ¹¹C-labelled PET tracers that could be used to study the pathophysiology of AD, to be used in the early or differential diagnosis or to be used in development of treatment and in monitoring of treatment effects.     

Evaluation of Wegener’s granulomatosis using 18F-fluorodeoxyglucose positron emission tomography/computed tomography

Objective

Wegener’s granulomatosis (WG) is a relatively rare disease characterized by granulomatous necrotizing vasculitis that primarily involves small- and medium-sized vessels. Systemic findings observed on ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) have not been well reported. The purpose of this study was to evaluate the FDG PET/CT imaging in the diagnosis and follow-up of patients with WG.

Materials and methods

Thirteen FDG PET/CT images obtained for 8 patients (2 men and 6 women) with WG were retrospectively analyzed. Of these, 6 were performed for diagnosis, 2 for restaging and follow-up, and 5 for assessment of treatment efficacy. Maximum standardized uptake values (max SUVs) and visual analyses were used to interpret the FDG PET/CT images. In addition, nonenhanced CT findings obtained during FDG PET/CT were described.

Results

WG lesions of the upper respiratory tract and lung were more clearly detected by FDG PET/CT fusion imaging than by nonenhanced CT alone, and all of the active lesions showed decreased FDG uptake after treatment. In addition, FDG PET/CT can provide complementary information to indicate biopsy site based on FDG uptakes.

Conclusions

FDG PET/CT is a feasible modality for evaluating lesion activities, therapeutic monitoring, and follow-up of WG. Furthermore, biopsy sites of WG lesions may be determined by FDG PET/CT.     

Does myocardial thallium-201 SPECT combined with electron beam computed tomography improve the detectability of coronary artery disease? —Comparative study of diagnostic accuracy—

Objective

The aim of this study is to evaluate the diagnostic accuracy of myocardial²⁰¹T1 SPECT combined with EBT for detecting CAD.

Methods

The study was based on 34 patients with suspected CAD, who had EBT and myocardial²⁰¹Tl SPECT. The CAD was diagnosed by the findings of coronary arteriography. Sensitivity, specificity and accuracy of EBT, myocardial²⁰¹Tl SPECT and the combined diagnosis on a per vessel basis and a per-patient basis were studied.

Results

The sensitivity for detecting CAD of myocardial²⁰¹Tl SPECT, EBT and the combined diagnosis was 85%, 77%, and 62%, respectively. No significant difference in the accuracy of myocardial²⁰¹T1 SPECT, EBT and the combined diagnosis was observed on a patient basis and per vessel basis. In the over 70 yr age subgroup, the sensitivity and accuracy of EBT for detecting LAD lesion were significantly superior to those of myocardial²⁰¹Tl SPECT. Regardless of age-based subgroups and gender, the combined diagnosis did not contribute to an improvement in diagnostic accuracy.

Conclusion

Although the sensitivity of EBT for detecting LAD lesion in patients over 70 yr of age was significantly higher than that of myocardial²⁰¹Tl SPECT, in the detectability of CAD, combined use of myocardial²⁰¹Tl SPECT and EBT offers no improvement.     

Myocardial sympathetic innervation in patients with chronic coronary artery disease: is reduction in coronary flow reserve correlated with sympathetic denervation?

Purpose Higher sensitivity of sympathetic nerves to ischaemia in comparison with myocytes has been observed and has been claimed to contribute to poor prognosis in patients with coronary artery disease (CAD). The aim of this study was to evaluate the dependency of myocardial sympathetic innervation on restrictions in coronary flow reserve (CFR). Methods We analysed 27 non-diabetic patients with advanced CAD. We determined quantitative myocardial blood flow using ¹³N-ammonia PET, myocardial viability with ¹⁸F-FDG PET and cardiac innervation with ¹¹C-HED PET. Scarred segments were excluded from analysis. We investigated the relationship between regional HED retention, blood flow and CFR. Results There was no correlation between rest perfusion and HED retention within a flow range from approximately 30 to 120 ml/(100 ml·min). A slight correlation was observed between stress perfusion values and HED retention (p<0.001), and between CFR and HED retention (p<0.001). Conclusion In non-diabetic CAD patients, HED retention in vital myocardium does not correlate with myocardial rest perfusion over a large flow range. The observed relation between HED retention and CFR indicates that sympathetic innervation can be preserved even when there is major impairment of myocardial blood supply. Most probably the occurrence of denervation depends not only on reductions in CFR, but also on the duration and severity of resulting ischaemic episodes.     

The optimal reference population for cardiac normality in myocardial SPET in the detection of coronary artery stenoses: patients with normal coronary angiography or subjects with low likelihood of coronary artery disease?

Both subjects with a low likelihood for coronary artery disease (CAD) and patients with normal findings on coronary angiography have been used as reference populations in non-invasive stress testing, including myocardial perfusion scintigraphy. Both of these criteria of normality - low likelihood of CAD and normal coronary angiography - have been criticised, and consensus on this issue is lacking. The aim of this study was to compare two different reference populations by testing the performance of artificial neural networks designed to interpret myocardial scintigrams. The networks were trained on myocardial perfusion scintigrams from 87 patients with angiographically documented CAD and on studies from one of two different reference groups: 48 patients with no signs of CAD based on angiography or 128 healthy volunteers with a likelihood for CAD <5%. The performance of the two different networks was then tested using scintigrams from a separate test group of 68 patients. Coronary angiography was used as the gold standard in this group. The network trained on patients with no signs of CAD based on angiography showed an area under the receiver operating characteristic (ROC) curve of 93%. The ROC area for the network trained on healthy volunteers was 72%, and this difference was statistically significant (P=0.03). The results of this study using artificial neural networks suggest that normal angiography should be preferred as the reference standard in myocardial scintigraphy when a patient is examined for CAD prior to possible angiography. Whether the same is true for other indications, e.g. in prognostic evaluation, is unknown.     

Detection of amyloid in Alzheimer’s disease with positron emission tomography using [11C]AZD2184

Purpose

Current positron emission tomography (PET) radioligands for detection of Aβ amyloid in Alzheimer’s disease (AD) are not ideal for quantification. To improve the signal to noise ratio we have developed the radioligand [¹¹C]AZD2184 and report here the first clinical evaluation.

Methods

Eight AD patients and four younger control subjects underwent 93-min PET measurements with [¹¹C]AZD2184. A ratio approach using the cerebellum as reference region was applied to determine binding parameters.

Results

Brain uptake of [¹¹C]AZD2184 peaked within 1 min at 3–4% of injected radioactivity. AD patients had high radioactivity in cortical regions while controls had uniformly low radioactivity uptake. Specific binding peaked within 30 min at which time standardized uptake value ratios (SUVR) ranged between 1.19 and 2.57.

Conclusion

[¹¹C]AZD2184 is a promising radioligand for detailed mapping of Aβ amyloid depositions in Alzheimer’s disease, due to low non-specific binding, high signal to background ratio and reversible binding as evident from early peak equilibrium.     

The optimal reference population for cardiac normality in myocardial SPET in the detection of coronary artery stenoses: patients with normal coronary angiography or subjects with low likelihood of coronary artery disease?

Both subjects with a low likelihood for coronary artery disease (CAD) and patients with normal findings on coronary angiography have been used as reference populations in non-invasive stress testing, including myocardial perfusion scintigraphy. Both of these criteria of normality--low likelihood of CAD and normal coronary angiography--have been criticised, and consensus on this issue is lacking. The aim of this study was to compare two different reference populations by testing the performance of artificial neural networks designed to interpret myocardial scintigrams. The networks were trained on myocardial perfusion scintigrams from 87 patients with angiographically documented CAD and on studies from one of two different reference groups: 48 patients with no signs of CAD based on angiography or 128 healthy volunteers with a likelihood for CAD <5%. The performance of the two different networks was then tested using scintigrams from a separate test group of 68 patients. Coronary angiography was used as the gold standard in this group. The network trained on patients with no signs of CAD based on angiography showed an area under the receiver operating characteristic (ROC) curve of 93%. The ROC area for the network trained on healthy volunteers was 72%, and this difference was statistically significant (P=0.03). The results of this study using artificial neural networks suggest that normal angiography should be preferred as the reference standard in myocardial scintigraphy when a patient is examined for CAD prior to possible angiography. Whether the same is true for other indications, e.g. in prognostic evaluation, is unknown.     

Evaluation of myocardial viability following acute myocardial infarctic using201Tl SPECT after thallium-glucose-insulin infusion —Comparison with18F-FDG positron emission tomography—

OBJECTIVE AND METHODS: The aim of this study was to evaluate myocardial viability in patients after acute myocardial infarction (AMI). We compared 201Tl SPECT after 201Tl with GIK (10% glucose 250 ml, insulin 5 U and KCl 10 mEq) infusion (GIK-201Tl) with resting 201Tl and 99mTc-pyrophosphate (PYP) dual SPECT, positron emission computed tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) in 21 patients with their first AMI, who all underwent successful reperfusion. GIK-201Tl SPECT, 201Tl and 99mTc-PYP dual SPECT were done within 10 days after admission and 18F-FDG-PET was performed at 3 weeks. GIK-201Tl SPECT was obtained after 30 min of GIK-201Tl infusion. 18F-FDG (370 MBq) was injected intravenously after oral glucose (1 g/ kg) loading, and then PET was obtained. PET and SPECT images were divided into 20 segments. Regional tracer uptake was scored using a 4-point scoring system (3 = normal to 0 = defect), and summed to a regional uptake score (RUS). Regional area means the infarcted area in which 99mTc-PYP accumulated. The number of decreased uptake segments (ES) was then determined. The infarcted area was defined as the area of 99mTc-PYP uptake. RESULTS: The ESs for the GIK-201Tl and 18F-FDG-PET images were significantly lower than the number of 99mTc-PYP uptake segments. The RUS for GIK-201Tl was higher than that for resting-201Tl imaging and similar to those for 18F-FDG-PET. CONCLUSIONS: In the detection of myocardial viability following AMI, GIK-201Tl imaging is useful with findings similar to those of 18F-FDG-PET.     

Does location matter? Prognostic value of single-photon emission computed tomography myocardial perfusion imaging by vascular territory

Background

The location of a myocardial perfusion abnormality frequently affects clinical decision making, especially if the left anterior descending artery (LAD) territory is involved. The purpose of this study was to determine whether the location of abnormalities on single-photon emission computed tomography (SPECT) imaging affects outcomes.

Methods

We retrospectively analyzed 21,294 consecutive patients with known or suspected coronary artery disease who underwent exercise or pharmacological stress SPECT over a 10-year period. Using the ASNC 17-segment model, 2 observers interpreted images with regards to defect severity, size, and reversibility. The summed stress score (SSS) was used in relation to vascular territories [LAD, right coronary artery (RCA), and left circumflex artery (LCx)]. All patients were followed over a mean period of 2.5?±?2?years for cardiac events (cardiac death or non-fatal myocardial infarction).

Results

Of the enrolled patients, 5,676 had single-vessel territory defects with a mean SSS of 4.3?±?2.8. Cardiac event-free survival curves revealed no significant difference between the 3 locations (LAD, RCA, and LCx) (P?=?.235). When compared by mild (2-3), moderate (4-8), or severe (>8) SSS, outcomes between the 3 groups were again similar. There were 2,907 patients with two-vessel territory defects with a mean SSS of 10.8. Outcomes were similar between the following 2 groups: two-vessel with LAD involvement and two-vessel without LAD involvement (P?=?.558).

Conclusion

In patients with single- or two-vessel territory perfusion abnormalities with similar size and severity of perfusion defects, the location of defect did not impact future cardiac events. Location of myocardial perfusion defect on SPECT imaging may not be helpful in clinical decision making.     

Non-invasive estimation of myocardial efficiency using positron emission tomography and carbon-11 acetate – comparison between the normal and failing human heart

The clearance kinetics of carbon-11 acetate, assessed by positron emission tomography (PET),can be combined with measurements of ventricular function for non-invasive estimation of myocardial oxygen consumption and efficiency. In the present study, this approach was applied to gain further insights into alterations in the failing heart by comparison with results obtained in normals. We studied ten patients with idiopathic dilated cardiomyopathy (DCM) and 11 healthy normals by dynamic PET with ¹¹C-acetate and either tomographic radionuclide ventriculography or cine magnetic resonance imaging. A ”stroke work index” (SWI) was calculated by: SWI = systolic blood pressure × stroke volume/body surface area. To estimate myocardial efficiency, a ”work-metabolic index” (WMI) was then obtained as follows: WMI = SWI × heart rate/k(mono), where k(mono) is the washout constant for ¹¹C-acetate derived from mono-exponential fitting. In DCM patients, left ventricular ejection fraction was 19%±10% and end-diastolic volume was 92±28 ml/m² (vs 64%±7% and 55±8 ml/m² in normals, P<0.001). Myocardial oxidative metabolism, reflected by k(mono), was significantly lower compared with that in normals (0.040±0.011/min vs 0.060± 0.015/min; P<0.003). The SWI (1674±761 vs 4736± 895 mmHg × ml/m²; P<0.001) and the WMI as an estimate of efficiency (2.98±1.30 vs 6.20±2.25×10⁶ mmHg × ml/m²; P<0.001) were lower in DCM patients, too. Overall, the WMI correlated positively with ejection parameters (r=0.73, P<0.001 for ejection fraction; r=0.93, P<0.001 for stroke volume), and inversely with systemic vascular resistance (r=–0.77; P<0.001). There was a weak positive correlation between WMI and end-diastolic volume in normals (r=0.45; P=0.17), while in DCM patients, a non-significant negative correlation coefficient (r=–0.21; P=0.57) was obtained. In conclusion non-invasive estimates of oxygen consumption and efficiency in the failing heart were reduced compared with those in normals. Estimates of efficiency increased with increasing contractile performance, and decreased with increasing ventricular afterload. In contrast to normals, the failing heart was not able to respond with an increase in efficiency to increasing ventricular volume. The present data support the usefulness of the WMI for non-invasive characterization of cardiac efficiency and may serve as a background for improved evaluation of medical therapy for heart failure. Received 10 August and in revised form 3 November 1999     

Is contrast material needed after treatment of malignant lymphoma in positron emission tomography/computed tomography?

Purpose  

Positron emission tomography (PET)/computed tomography (CT) with ¹⁸F-fluorodeoxyglucose is widely used for post-therapeutic surveillance of malignant lymphoma. Debate still exists as to whether intravenous contrast media during the CT stage of a PET/CT scan should be used. The purpose of this study was to investigate the clinical value of contrast agent in PET/CT in patients with lymphoma following treatment.     

Estimation of coronary flow reserve: Can SPECT compete with other modalities?

Conclusion  SPECT can obtain CFR measurements, both globally and regionally. Positive SPECT results, as well as positive PET results, depend upon the tracer having a constant extraction fraction over the flow range being studied. SPECT approaches will probably not be as accurate as dynamic PET for estimation of CFR because spatial and timing resolution is poorer. Also, the radiopharmaceuticals may not track flow as effectively as O-15 water. The method presented by Sugihara et al is simpler than dynamic cardiac SPECT with compartment modeling; however, the technique works only for radiopharmaceuticals that act like microspheres. It is important that the extraction remain constant over a large flow range. The microsphere method also relies on not having any wash-out from the tissue from the time of injection to the time of measurement. Dynamic cardiac SPECT works best with radiopharmaceuticals that have high extraction. These radiopharmaceuticals are not as fast as the ideal flow tracer O-15 water. However, because of the inadequate timing resolutions of commercial SPECT systems, it would be virtually impossible to image such flow tracers. Research is still needed in the following areas. (1) Further studies should be done to determine what mechanisms govern maximal coronary vasodilation. (2) There should be a determination of how these new SPECT approaches can be evaluated and tested in human beings. It has yet to be determined whether use of the coronary flow or pressure wire would be better. Perhaps comparison to dynamic PET imaging alone would be sufficient. (3) Systematic studies should be done to define the distribution of absolute CFR in both normal and abnormal hearts and to determine how the common factors that can diminish CFR affect regional reserve, especially in small subendocardial regions. To truly define coronary vascular reserve, it is essential that subendocardial measurements of CFR be obtainable. (4) Technological advances must be made in order to improve SPECT imaging systems so that they better facilitate dynamic imaging. Current SPECT systems have been limited by low sensitivity, poor resolution, and poor temporal resolution as a result of the necessary mechanical rotation of the detector. However, recent advancements in dynamic cardiac SPECT, drawn from developments in PET, demonstrate that dynamic cardiac SPECT is useful for the extraction of physiologic values of perfusion38 in a manner similar to that of dynamic PET. These systems allow volumetric imaging but do not require sampling at rates of less than 5 seconds because of the lack of sufficient statistical data.     

Characterization of idiopathic Parkinson’s disease subgroups using quantitative gait analysis and corresponding subregional striatal uptake visualized using 18F-FP-CIT positron emission tomography

BackgroundGait disturbance is one of the most common symptoms among patients with idiopathic Parkinson’s disease (IPD). Nevertheless, Parkinson’s disease subtype clustering according to gait characteristics has not been thoroughly investigated.Research questionThe aim of this study was to identify subgroups according to gait pattern among patients with IPD.MethodsThis study included 88 patients with IPD who underwent ¹⁸F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-4-iodophenyl-nortropane positron emission tomography (¹⁸F-FP-CIT PET) and three-dimensional gait analysis (3DGA) between January 1, 2014 and December 31, 2016. We performed cluster analysis using temporal-spatial gait variables (gait speed, stride length, cadence, and step width) and divided patients into four subgroups. The kinematic and kinetic gait variables in 3DGA were compared among the four subgroups. Furthermore, we compared the uptake patterns of striatum among the four subgroups using ¹⁸F-FP-CIT PET.ResultsThe patients were clustered into subgroups based on gait hypokinesia and cadence compensation. Group 1 had decreased stride length compensating with increased cadence. Group 2 had decreased stride length without cadence compensation and wider step width. Group 3 had relatively spared stride length with decreased cadence. Group 4 had spared stride length and cadence. The uptake of posterior putamen was significantly decreased in Group 3 compared with Group 4.SignificanceGait hypokinesia and cadence can help to classify gait patterns in IPD patients. Our subgroups may reflect the different gait patterns in IPD patients.     

Coronary artery disease: Which degree of coronary artery stenosis is indicative of ischemia?

Purpose

To prospectively determine the best cut-off value of stenosis degree for low-dose computed tomography coronary angiography (CTCA) to predict the hemodynamic significance of coronary artery stenoses compared to catheter angiography (CA) using a cardiac magnetic resonance based approach as standard of reference.

Materials and methods

Fifty-two patients (mean age, 64 ± 10 years) scheduled for CA underwent cardiac magnetic resonance (CMR) at 1.5-T and dual-source CTCA using prospective ECG-triggering the same day. Diagnostic performance of CTCA and CA to detect myocardial ischemia was evaluated with CMR as the standard of reference. The diagnostic performance and best cut-off values to predict the hemodynamic significance of coronary were determined from receiver operating characteristics analysis (ROC).

Results

CA revealed >50% stenoses in 131/832 segments (15.7%) in 78/156 (50.0%) coronary arteries in 32/52 (62%) patients. CTCA revealed >50% stenoses in 148/807 (18.3%) segments, corresponding to 83/156 (53.2%) coronary arteries in 34/52 (65.4%) patients. CMR revealed ischemia in 118/832 (14.2%) myocardial segments corresponding to the territories of 60/156 (38.5%) coronary arteries in 29/52 (56%) patients. ROC analysis showed equal diagnostic performance for low-dose CTCA and CA with areas under the curve (AUC) of 0.82 and 0.83 (P = 0.64). The optimal cut-off value was determined at stenosis of >60% for the prediction of hemodynamically significant coronary stenosis by CTCA. Using this cut-off value, sensitivity, specificity, NPV and PPV to predict hemodynamic significance by CTCA were 100%, 83%, 100%, and 88% on a per-patient basis and 88%, 73%, 83% and 81% on a per-artery analysis, respectively.

Conclusion

By considering coronary stenosis >60%, diagnostic performance for predicting the hemodynamic significance of coronary stenosis by CTCA is optimal and equals that of CA.     

Extrastriatal spreading of microglial activation in Parkinson’s disease: a positron emission tomography study

Background

The neuroinflammatory glial response contributes to the degenerative process in Parkinson’s disease (PD). However, the pattern of microglial progression remains unclear.

Methods

We evaluated microglial activation in early stage PD patients by quantifying changes in neuroinflammation using PET with [¹¹C]DPA713, a selective PET tracer for microglial activation. Eleven PD patients (Hoehn and Yahr stages 1–2) without dementia underwent the [¹¹C]DPA713 PET scan two times with 1 year apart. The binding potential (BP_ND) was estimated with the simplified reference tissue model. Voxelwise and regions of interest analyses were used to compare the regional BP_ND among groups.

Results

Significant increase in [¹¹C]DPA713 BP_ND was found extrastriatally in the occipital, temporal and parietal cortex in PD patients, and the degree of BP_ND became much higher over the brain regions predominantly in the temporal and occipital cortex 1 year later.

Conclusion

The current results indicated that an extrastriatal spreading of microglial activation reflects one of PD pathophysiology occurring at an early stage.

     

The clinical value of single photon emission computed tomography myocardial perfusion imaging in cardiac risk stratification of very elderly patients (≥80 years) with suspected coronary artery disease

Background  

The role of single photon emission computed tomography myocardial perfusion imaging (SPECT MPI) in cardiac evaluation of the very elderly patients is unclear. We investigated the clinical value of SPECT MPI in very elderly patients (≥80 years) with suspected coronary artery disease (CAD) as well as in comparison to younger patients.