The accuracy of quantitative parameters in (99m) Tc-MAG3 dynamic renography: a national audit based on virtual image data.

Assessment of image analysis methods and computer software used in (99m) Tc-MAG3 dynamic renography is important to ensure reliable study results and ultimately the best possible care for patients. In this work, we present a national multicentre study of the quantification accuracy in (99m) Tc-MAG3 renography, utilizing virtual dynamic scintigraphic data obtained by Monte Carlo-simulated scintillation camera imaging of digital phantoms with time-varying activity distributions. Three digital phantom studies were distributed to the participating departments, and quantitative evaluation was performed with standard clinical software according to local routines. The differential renal function (DRF) and time to maximum renal activity (Tmax ) were reported by 21 of the 28 Swedish departments performing (99m) Tc-MAG3 studies as of 2012. The reported DRF estimates showed a significantly lower precision for the phantom with impaired renal uptake than for the phantom with normal uptake. The Tmax estimates showed a similar trend, but the difference was only significant for the right kidney. There was a significant bias in the measured DRF for all phantoms caused by different positions of the left and right kidney in the anterior-posterior direction. In conclusion, this study shows that virtual scintigraphic studies are applicable for quality assurance and that there is a considerable uncertainty associated with standard quantitative parameters in dynamic (99m) Tc-MAG3 renography, especially for patients with impaired renal function.

Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours.

AIM: To study histidine decarboxylase (HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus (n = 3) and corpus (n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours (GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2 (VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid (U-MeImAA) was determined using high-performance liquid chromatography in 27 of the 64 patients. RESULTS: In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cell population co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-MeImAA excretion was detected, but only two of the patients exhibited related endocrine symptoms. CONCLUSION: Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Co-expression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.

How to measure renal artery stenosis--a retrospective comparison of morphological measurement approaches in relation to hemodynamic significance.

BACKGROUND: Although it is well known that renal artery stenosis may cause renovascular hypertension, it is unclear how the degree of stenosis should best be measured in morphological images. The aim of this study was to determine which morphological measures from Computed Tomography Angiography (CTA) and Magnetic Resonance Angiography (MRA) are best in predicting whether a renal artery stenosis is hemodynamically significant or not. METHODS: Forty-seven patients with hypertension and a clinical suspicion of renovascular hypertension were examined with CTA, MRA, captopril-enhanced renography (CER) and captopril test (Ctest). CTA and MRA images of the renal arteries were analyzed by two readers using interactive vessel segmentation software. The measures included minimum diameter, minimum area, diameter reduction and area reduction. In addition, two radiologists visually judged the diameter reduction without automated segmentation. The results were then compared using limits of agreement and intra-class correlation, and correlated with the results from CER combined with Ctest (which were used as standard of reference) using receiver operating characteristics (ROC) analysis. RESULTS: A total of 68 kidneys had all three investigations (CTA, MRA and CER + Ctest), where 11 kidneys (16.2 %) got a positive result on the CER + Ctest. The greatest area under ROC curve (AUROC) was found for the area reduction on MRA, with a value of 0.91 (95 % confidence interval 0.82-0.99), excluding accessory renal arteries. As comparison, the AUROC for the radiologists' visual assessments on CTA and MRA were 0.90 (0.82-0.98) and 0.91 (0.83-0.99) respectively. None of the differences were statistically significant. CONCLUSIONS: No significant differences were found between the morphological measures in their ability to predict hemodynamically significant stenosis, but a tendency of MRA having higher AUROC than CTA. There was no significant difference between measurements made by the radiologists and measurements made with fuzzy connectedness segmentation. Further studies are required to definitely identify the optimal measurement approach.

Comparison between visual assessment of dopaminergic degeneration pattern and semi-quantitative ratio calculations in patients with Parkinson's disease and Atypical Parkinsonian syndromes using DaTSCAN® SPECT.

OBJECTIVE: To verify if (123)I-FP-CIT, DaTSCAN(®) can differentiate early stages of Parkinson's disease (PD) as well as patients with Atypical Parkinsonian syndromes (APS) from manifest Parkinson's disease. METHODS: 128 consecutive patients were investigated with (123)I-FP-CIT SPECT during a 4-year period. All patients were diagnosed according to the established consensus criteria for diagnosis of PD (n = 53) and APS (n = 19). Remaining patients were grouped early PD (before onset of L-DOPA medication), (n = 20), vascular PD (n = 6), and non-PD syndromes (n = 30) and SWEDD (n = 1). SPECT images were analyzed visually according to a predefined ranking scale of dopaminergic nerve cell degeneration, distinguishing a posterior-anterior degeneration pattern (egg shape) from a more global and severe degeneration pattern (burst striatum). Striatum uptake ratios were quantitatively analyzed with the 3D software, EXINI. RESULTS: In the group of APS patients, the burst striatum pattern was most frequent and found in 61 % (11/18 patients). In PD patients, the egg shape pattern was dominating, especially in early PD where it was present in 95 % (19/20 patients). The positive predictive value for the egg shape pattern to diagnose PD was 92 % in this material (APS and all PD patients) and the specificity 90 % for the burst striatum pattern to exclude APS. The uptake ratios were reduced in both PD and APS patients and closely related to the image ranking. CONCLUSION: In this study, we found that in more than half of the patients it was possible to differentiate between PD and APS by visual interpretation only. Similar results were obtained using semi-quantitative uptake ratios. Combining visual assessment with uptake ratios did not add to the discriminating power of DaTSCAN(®) SPECT in this material.

Urinary excretion of histamine and methylhistamine after burns.

BACKGROUND: The increased vascular permeability seen after burn contribute to morbidity and mortality as it interferes with organ function and the healing process. Large efforts have been made to explore underlying pathophysiological mechanisms that generate increased vascular permeability after burns. Many different substances have been proposed as mediators of which histamine, serotonin and oxygen radicals are claimed most important. However, no specific blocker has convincingly been shown to be clinically effective. Early work has claimed increased histamine plasma-concentrations in humans after burn and data from animal models pointed at histamine as an important mediator. Modern human clinical studies investigating the role of histamine as a mediator of the generalized post burn increase in vascular permeability are lacking. METHOD: We examined histamine turnover by measuring the urinary excretion of histamine and methyl histamine for 48 h after burns in 8 patients (mean total burn surface area 24%). RESULTS: Over time, in this time frame and compared to healthy controls we found a small increase in the excretion of histamine, but no increase of its metabolite methylhistamine. CONCLUSION: Our findings do not support that histamine is an important mediator of the increased systemic vascular permeability seen after burn.

Non-invasive investigations of potential renal artery stenosis in renal insufficiency.

BACKGROUND: The diagnostic value of non-invasive methods for diagnosing renal artery stenosis in patients with renal insufficiency is incompletely known. METHODS: Forty-seven consecutive patients with moderately impaired renal function and a clinical suspicion of renal artery stenosis were investigated with computed tomography angiography (CTA), gadolinium-enhanced magnetic resonance angiography (MRA), contrast-enhanced Doppler ultrasound and captopril renography. The primary reference standard was stenosis reducing the vessel diameter by at least 50% on CTA, and an alternative reference standard ('morphological and functional stenosis') was defined as at least 50% diameter reduction on CTA or MRA, combined with a positive finding from ultrasound or captopril renography. RESULTS: The frequency of positive findings, calculated on the basis of individual patients, was 70% for CTA, 60% for MRA, 53% for ultrasound and 30% for captopril renography. Counting kidneys rather than patients, corresponding frequencies were 53%, 41%, 29% and 15%, respectively. In relation to the CTA standard, the sensitivity (and specificity) at the patient level was 0.81 (0.79) for MRA, 0.70 (0.89) for ultrasound and 0.42 (1.00) for captopril renography, and at the kidney level 0.76 (0.82), 0.53 (0.81) and 0.30 (0.86), respectively. Relative to the alternative reference standard, corresponding values at the patient level were 1.00 (0.62) for CTA, 0.90 (0.69) for MRA, 0.91 (1.00) for ultrasound and 0.67 (1.00) for captopril renography, and at the kidney level 0.96 (0.76), 0.85 (0.79), 0.71 (0.97) and 0.50 (0.97), respectively. CONCLUSIONS: CTA and MRA are superior to ultrasound and captopril renography at diagnosing morphological stenosis, but ultrasound may be useful as a screening method and captopril renography for verifying renin-dependent hypertension.

HMPAO SPECT in Parkinson's disease (PD) with major depression (MD) before and after antidepressant treatment.

Previously we suggested that major depression (MD) in Parkinson's disease (PD) could be an indication of a more advanced and widespread neurodegenerative process, as PD symptoms were more severe in those with depression. We also found a different antidepressant response with SSRI medication in PD patients with depression compared to depressed patients without PD. This indicates diverse underlying pathophysiological mechanisms. Investigations using single-photon emission computed tomography (SPECT), measuring regional cerebral blood flow (rCBF), may contribute to enlighten the neurobiological substrates linked to depressive symptoms. SPECT was performed in order to compare rCBF in MD patients with and without PD. The study included 11 MD patients with PD, 14 non-depressed PD patients and 12 MD patients without PD. All patients were followed for 12 weeks with repeated evaluation of depressive as well as PD symptoms. Anti-Parkinsonian treatment remained unchanged during the study. Antidepressant treatment with SSRI (citalopram) was given to all patients with MD. SPECT was performed before and after 12 weeks of antidepressant treatment. rCBF was found to differ between PD patients with and without MD, as well as between MD patients with and without PD, both at baseline and concerning the response to treatment with SSRI (citalopram). In patients with PD the rCBF was found to be decreased in preoccipital and occipital regions, a finding more common when PD was combined with MD. In summary, larger cortical areas were found to be involved in depressed PD patients, both with hyperactivity (reciprocal to basal degeneration in PD and maybe dopaminergic treatment) and with hypoactivity (probably due to organic lesions leading to hypoperfusion). These observations support our hypothesis that PD combined with MD is an expression of a more advanced and widespread neurodegenerative disorder.

Advantages of standardized criteria for the interpretation of angiotensin-converting enzyme inhibition renography.

BACKGROUND: The aim of this study was to evaluate the efficiency of captopril renography to detect renovascular hypertension (RVH) using the standardized test criteria established at the consensus conference in Santa Fe 1995. The evaluation was made prospectively and in a clinical situation. METHODS: Renal scintigraphy was performed with Tc-MAG3 according to a 2-day protocol in patients receiving 25 mg captopril 1 h before the test. A baseline study was added only in patients showing abnormal findings in the captopril-stimulated study. All tests were re-evaluated according to the consensus criteria by two nuclear medicine specialists who were unaware of the original evaluation that was made by different doctors on duty at the nuclear medicine section at the time. RESULTS: Using a 12-month clinical follow-up as a reference, 16 patients in a group of 164 hypertensive patients had RVH, that is, a prevalence of 10%. The re-evaluation and original evaluation indicated a sensitivity of 94 versus 100%, specificity of 97 versus 88%, accuracy of 97 versus 89%, positive predictive value of 83 versus 47%, and negative predictive value of 99 versus 100%. In 15 studies, results from the two evaluations were discordant and in 14 of these studies an originally false positive or intermediate study was re-evaluated as negative. The test result was highly decisive in the future management of patients, minimizing the number of renal angiograms that had to be performed and initiating a search for other causes of secondary hypertension. CONCLUSION: Captopril renography is a useful and reliable test in patients with suspicion of RVH. Strict adherence to the diagnostic criteria and recommendations from the 1995 consensus conference further improved the performance of the test compared with clinical follow-up.

Leukocyte scintigraphy compared to intraoperative small bowel enteroscopy and laparotomy findings in Crohn's disease.

BACKGROUND: Leukocyte scintigraphy is a noninvasive investigation to assess inflammation. We evaluated the utility of labeled leukocytes to detect small bowel inflammation and disease complications in Crohn's disease and compared it to whole small bowel enteroscopy and laparotomy findings. METHODS: Scintigraphy with technetium-99m exametazime-labeled leukocytes was prospectively performed in 48 patients with Crohn's disease a few days before laparotomy; 41 also had an intraoperative small bowel enteroscopy. The same procedures were performed in 8 control patients. Independent grading of scans was compared with the results of enteroscopy and with surgical, histopathologic, and clinical data. RESULTS: In the 8 control patients leukocyte scan, endoscopy, and histopathology were all negative for the small bowel. In patients with Crohn's disease and small bowel inflammation seen at enteroscopy and/or laparotomy (n = 39) the scan was positive in 33. In 8 patients without macroscopic small bowel inflammation, the scan was positive for the small bowel in 3 patients; at histology, 2 of 3 had inflammation. When combining results for patients and controls, the sensitivity of leukocyte scan for macroscopically evident small bowel inflammation was 0.85, specificity 0.81, accuracy 0.84, positive predictive value 0.92, and negative predictive value 0.68. Scintigraphy detected inflammatory lesions not known before laparotomy in 16 of 47 (34%) Crohn's disease patients and showed uptake in 25 of 35 (71%) bowel strictures. It was diagnostic regarding 4 of 8 abscesses and 9 of 15 fistulas. In 6 patients (13%) lesions first demonstrated by leukocyte scintigraphy were treated during the surgery performed. CONCLUSIONS: Leukocyte scintigraphy reliably detects small bowel inflammation in Crohn's disease. It gives additional information on the presence of inflammatory lesions in a fraction of patients planned for surgery.

Interpretation of captopril renography using artificial neural networks.

The purpose of this study was to develop a method based on artificial neural networks for interpretation of captopril renography tests for the detection of renovascular hypertension caused by renal artery stenosis and to assess the value of different measurements from the test. A total of 250 99mTc-MAG3 captopril renography tests were used in the study. The material was collected from two different patient groups. One group consisted of 101 patients who also had undergone a renal angiography. The angiographies, which were used as gold standard, showed a significant renal artery stenosis in 53 of the 101 cases. The second group consisted of 149 patients, who's captopril renography tests all were interpreted as not compatible with significant renal artery stenosis by an experienced nuclear medicine physician. Artificial neural networks were trained for the diagnosis of renal artery stenosis using eight measures from each renogram. The neural network was then evaluated in separate test groups using an eightfold cross validation procedure. The performance of the neural networks, measured as the area under the receiver operating characteristic curve, was 0.93. The sensitivity was 91% at a specificity of 90%. The lowest performance was found for the network trained without use of a parenchymal transit measure, indicating the importance of this feature. Artificial neural networks can be trained to interpret captopril renography tests for detection of renovascular hypertension caused by renal artery stenosis. The result almost equals that of human experts shown in previous studies.

Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type.

OBJECTIVE: To analyze tumor biology and the outcome of differentiated treatment in relation to tumor subtype in patients with gastric carcinoid. BACKGROUND: Gastric carcinoids may be subdivided into ECL cell carcinoids (type 1 associated with atrophic gastritis, type 2 associated with gastrinoma, type 3 without predisposing conditions) and miscellaneous types (type 4). The biologic behavior and prognosis vary considerably in relation to type. METHODS: A total of 65 patients from 24 hospitals (51 type 1, 1 type 2, 4 type 3, and 9 type 4) were included. Management recommendations were issued for newly diagnosed cases, that is, endoscopic or surgical treatment of type 1 and 2 carcinoids (including antrectomy to abolish hypergastrinemia) and radical resection for type 3 and 4 carcinoids. RESULTS: Infiltration beyond the submucosa occurred in 9 of 51 type 1, 4 of 4 type 3, and 7 of 9 type 4 carcinoids. Metastases occurred in 4 of 51 type 1 (3 regional lymph nodes, 1 liver), the single type 2 (regional lymph nodes), 3 of 4 type 3 (all liver), and 7 of 9 type 4 carcinoids (all liver). Of the patients with type 1 carcinoid, 3 had no specific treatment, 40 were treated with endoscopic or surgical excision (in 10 cases combined with antrectomy), 7 underwent total gastrectomy, and 1 underwent proximal gastric resection. Radical tumor removal was not possible in 2 of 4 patients with type 3 and 7 of 9 patients with type 4 carcinoid. Five- and 10-year crude survival rates were 96.1% and 73.9% for type 1 (not different from the general population), but only 33.3% and 22.2% for type 4 carcinoids. CONCLUSION: Subtyping of gastric carcinoids is helpful in the prediction of malignant potential and long-term survival and is a guide to management. Long-term survival did not differ from that of the general population regarding type 1 carcinoids but was poor regarding type 4 carcinoids.

The effect of percutaneous dilatation of renal arterial stenosis on captopril renography in hypertension.

BACKGROUND: The clinical effects of percutaneous transluminal renal artery angioplasty (PTRA) in patients with renal vascular stenosis and hypertension is controversial. METHODS: We consecutively recruited all 23 patients referred for evaluation of renovascular hypertension that eventually underwent unilateral PTRA, to be investigated with captopril MAG3 renography (CR), both before and after the endovascular procedure. Data were evaluated on an intention-to-treat basis. RESULTS: We found that the relative MAG3 clearance of the stenotic kidney increased (from 29.9+/-14% to 35.1+/-14%, p=0.01) and that the creatinine levels fell following the intervention (from 110+/-19 to 99+/-17 micromol/l, p=0.0003). Blood pressure levels were also lowered (from 173+/-32/93+/-17 to 158+/-31/86+/-15 mmHg, p<0.006) while the mean number of anti-hypertensive drugs was unchanged following PTRA (2.9+/-1.4 before and 2.8+/-1.3 drugs after the intervention, respectively, p=0.6). CONCLUSION: This prospective trial showed statistically significant improvements of individual kidney function as measured by CR and blood pressure in subjects with suspected renovascular hypertension treated with PTRA. Although the endovascular procedure was found to be safe, the magnitude of the absolute improvements was rather modest.

A computerized human reference brain for rCBF/SPET technetium-99m exametazime (HMPAO) investigation of elderly.

Using the bull's eye approach, a reference brain from the single photon emission tomography (SPET) images of 10 subjects aged 62-81 years with excellent mental and physical health was constructed. SPET images were acquired twice, 1 week apart, using a single detector rotating gamma camera collecting 64 planar images over a 360 degrees orbit. The centre of each transaxial slice was first defined with an automatic edge detecting algorithm applied to an anterior-posterior and a side profile of the brain. Each slice was divided into 40 sectors. Maximum counts/pixel in each sector was picked. The 40 maximum count values from one transaxial slice were allowed to form a horizontal row in a new parametric image on the x-axis and slice number from the vertex to the basal parts of the brain on the y-axis. This new image was scaled to a 64 x 16 pixel matrix by interpolation, which meant a normalization of all studies to the same size. The parametric image in each subject was scaled with regard to intensity by a factor calculated by a normalization procedure using the least squares analysis. Mean and SD for each pixel were calculated, thereby constructing a "mean parametric image", and a "SD parametric image". These two images are meant to be used as the reference brain for evaluation of patient studies. This method can be used for objective measurements of diffuse brain changes and for pattern recognition in larger groups of patients. Statistical multifactorial analysis of parameters used for acquisition and data processing is possible.