Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma.

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision of whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method for determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histologic nodal staging and avoids overtreating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This document is designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. Preparation of this guideline was carried out by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial (SENT) Committee.

Accurate geometric calibration in stepping-table digital subtraction angiography.

Accurate measurements of vessel dimensions are desirable in many clinical applications. This work uses the known relative motion between X-ray source and the patient in stepping-table digital subtraction angiography (DSA) to provide an accurate geometric calibration for quantitative measurements. The method results in a calibration factor that converts the size of the object measured in pixels on the image to its size in millimetres. The main sources of error relate to: (i) the assessment of relative displacement of a structure in a series of images; (ii) patient motion throughout data acquisition; and (iii) image distortion. Error was evaluated both with a test object consisting of a large grid of ball bearings (2x2 cm spaced) and, in vivo, in five renal DSA examinations performed with identical catheters of known diameter. The calibration factor was calculated with 0.1% accuracy for the test object and at least 2% accuracy in vivo, even with breath holding and pulsatile motion. This demonstrates that the calculation of the calibration factor can be very accurate, and that the method we propose is capable of the submillimetre accuracy required for clinical studies if used in conjunction with an accurate measurement of the vessel size in pixels. In conclusion, accurate geometric measurements can be performed in stepping-table DSA, without the need for external reference objects.

Highlights of the European Association of Nuclear Medicine Congress, Athens, Greece, 30 September to 4 October 2006.

The 2006 EANM Congress, held in Athens, Greece, was once again a major event in the nuclear medicine scientific and educational calendar. The scientific programme, which included the second biennial ISRTRD meeting, confirmed the major developments taking place in (1) the diagnostic and prognostic uses of nuclear medicine imaging (both in PET and in single-photon studies), (2) radionuclide therapies, (3) radiochemistry and radiopharmacy, and (4) physics. This paper outlines the major findings in each of these areas.

The addition of computer simulated noise to investigate radiation dose and image quality in images with spatial correlation of statistical noise: an example application to X-ray CT of the brain.

This study validates a method to add spatially correlated statistical noise to an image, applied to transaxial X-ray CT images of the head to simulate exposure reduction by up to 50%. 23 patients undergoing routine head CT had three additional slices acquired for validation purposes, two at the same clinical 420 mAs exposure and one at 300 mAs. Images at the level of the cerebrospinal fluid filled ventricles gave readings of noise from a single image, with subtraction of image pairs to obtain noise readings from non-uniform tissue regions. The spatial correlation of the noise was determined and added to the acquired 420 mAs image to simulate images at 340 mAs, 300 mAs, 260 mAs and 210 mAs. Two radiologists assessed the images, finding little difference between the 300 mAs simulated and acquired images. The presence of periventricular low density lesions (PVLD) was used as an example of the effect of simulated dose reduction on diagnostic accuracy, and visualization of the internal capsule was used as a measure of image quality. Diagnostic accuracy for the diagnosis of PVLD did not fall significantly even down to 210 mAs, though visualization of the internal capsule was poorer at lower exposure. Further work is needed to investigate means of measuring statistical noise without the need for uniform tissue areas, or image pairs. This technique has been shown to allow sufficiently accurate simulation of dose reduction and image quality degradation, even when the statistical noise is spatially correlated.

Contrast-enhanced magnetic resonance angiography of the iliac arteries: optimization by injection simulation.

Protocols for contrast-enhanced magnetic resonance angiography (CE-MRA) of the iliac arteries were optimized by computer simulations based on an impulse response function (IRF) of contrast agent (CA) concentration as a function of time obtained for 20 patients. Protocols with sequential, centric, and elliptical k-space coverage, different repetition rates (5 and 10 ms), and CA doses (0.1, 0.2, and 0.3 mmol/kg b.w.) were compared in terms of signal-to-noise ratio (SNR), distortion of vessel profiles, and sensitivity to timing errors. IRF-based simulations successfully characterized CA recirculation. Slow-rate CA infusions were found to achieve relatively high enhancement. In terms of SNR, there is no advantage in increasing the repetition rate. Distortion of vessel profiles is more likely in elliptic and centric k-space coverage. Protocols based on sequential k-space coverage and relatively long CA infusions proved to be particularly suited to large-FOV iliac examinations as they are relatively insensitive to timing errors.

Performance assessment of a slat gamma camera collimator for 511 keV imaging.

The physical performance of a prototype slat collimator is described for gamma camera planar imaging at 511 keV. Measurements were made of sensitivity, spatial resolution and a septal penetration index at 511 keV. These measurements were repeated with a commercial parallel hole collimator designed for 511 keV imaging. The slat collimator sensitivity was 22.9 times that of the parallel hole collimator with 10 cm tissue equivalent scatter material, and 16.8 times the parallel hole collimator sensitivity in air. Spatial resolution was also better for the slat collimator than the parallel hole collimator (FWHM at 10 cm in air 17.9 mm and 21.2 mm respectively). Septal penetration was compared by a single value for the counts at 120 mm from the point source profile peak, expressed as a percentage of the peak counts, showing less penetration for the slat collimator than the parallel hole collimator (1.9% versus 3.6% respectively). In conclusion, these results show that the slat collimator may have advantages over the parallel hole collimator for 511 keV imaging, though the greater complexity of operation of the slat collimator and potential sources of artefact in slat collimator imaging are recognized.

Inter-observer reproducibility of quantitative radionuclide colonic transit imaging.

The colonic transit of an indium-111 enteric coated capsule was imaged with a gamma camera over a period of 3 days. The geometric centre of activity in the colon was calculated from regions drawn over four segments of the colon, plus a fifth segment as the estimated passed stool activity. Fifteen healthy subjects were scanned and the results analysed. The images were analysed by two observers to assess reproducibility of the geometric centre quantitative index (correlation, r = 0.985). In conclusion, although it can be difficult to identify the anatomical segments of the colon from the gamma camera images, by following a protocol with clear guidelines for ROI placement, good inter-observer reproducibility can be obtained.

Moving segments region of interest attenuator for x-ray fluoroscopy.

Region of interest (ROI) imaging has previously been proposed as a means of reducing x-ray fluoroscopy radiation dose. Previous ROI attenuators made of partially attenuating metal plates change beam quality, which may lead to uncertainty in image restoration procedures. The design and construction of a prototype moving segments ROI attenuator (MS-ROI), which maintains beam quality across the whole field of view is described. The x-ray beam intensity is halved by 36 lead segments which are rapidly rotated between the x-ray tube and patient, with a central hole projecting a circular ROI at full intensity. Image processing techniques with automatic detection of the ROI boundary were used to homogenize image brightness across the whole image. Images restored using these techniques were judged to be visually acceptable, with a good match between pixel values inside and outside the ROI. Image contrast within the ROI was improved by 18% due to reduced scatter and veiling glare from the periphery. The introduction of the MS-ROI attenuator also results in a 48% increase in statistical noise in the area outside the ROI, with no significant change in object contrast. The patient entrance dose measured using the dose area product (DAP) method was reduced by 53.4% under manual exposure control, with the dose to operators reduced by 48.4% under automatic brightness control. Further work is needed to determine whether the attenuator can be used with pulsed fluoroscopy, and to reduce vibrational effects on the ROI boundary. The MS-ROI attenuator provides a more constant ratio of central-to-peripheral image intensity, and maintains uniform beam quality and image contrast across the whole image in comparison to simple metal plate attenuators.

A method to evaluate intra-operative gamma probes for sentinel lymph node localisation.

A method is described to allow objective evaluation of intra-operative gamma probe performance for the task of sentinel lymph node localisation. The method uses simple simulation based upon standard sensitivity and spatial resolution measurements at depth in water, with technetium-99m sources. The aim is to predict the minimum separation between the injection site and lymph node required to allow the sentinel lymph node to be identified in the presence of high injection site activity. The simulation methodology allows rapid investigation of probe performance for a range of node and injection site activities, and a range of node and injection site depths, without the need to perform a large number of physical measurements. Examples of practical performance simulations are given from five probes, showing that nodes at less than 115 mm from the injection site may be poorly localised, with even the best performing probe requiring at least 51 mm separation to allow detection in the high background from the injection site. This method provides data to allow the ranking of probe system performance in terms of the practical task of sentinel lymph node localisation, rather than arbitrary ranking based upon basic physical performance measures such as spatial resolution and sensitivity. The best probes allow sentinel lymph node localisation at between 20 and 30 mm closer to the injection site than the poorest performing probes, for situations which represent intra-operative localisation in melanoma and breast surgery. The method is also shown to assist in optimising system settings such as energy detection thresholds, and may allow users to understand the limitations and capabilities of intra-operative gamma probes.

Motion detection and correction using multi-rotation 180 degrees single-photon emission tomography for thallium myocardial imaging.

Patient and organ motion is a potentially limiting factor in gamma camera single-photon emission tomography (SPET) imaging, as highlighted in stress thallium myocardial SPET, where the heart may exhibit a systematic axial motion (cardiac creep) following stress. Multi-rotation SPET has previously been described as a means of obtaining better raw data for motion detection and correction. This study describes the validation of a computerised motion detection algorithm applied to multi-rotation SPET, and reports measured motions in thallium myocardial stress SPET studies from a single-headed gamma camera. Forty-two patients underwent pharmacological stress (dipyridamole) with leg raising, with injection of 75 MBq thallium-201 and imaging after a 10-min delay to detect or evaluate coronary artery disease. Multi-rotation gamma camera SPET was performed with a single-headed gamma camera, with five sequential rapid (4.5 min) continuous SPET mode rotations over 180 degrees. A one-dimensional cross-correlation alignment technique was applied to the projection images to perform motion detection and correction in the axial direction prior to combining the five data sets for tomographic reconstruction. Validation of the cross-correlation alignment analysis was carried out by performing imaging with measured whole-body axial motions in nine subjects, and by reproducibility measurements on multi-rotation data sets. The effect of the applied motion correction was evaluated by calculating mean differences between image pairs before and after shifting, and the general reliability of the automatic motion detection was checked to within one pixel by visual assessment of 160 image pairs. Validation measurements of the cross-correlation technique gave a mean absolute error of 1.5+/-0.4 mm (0.24+/-0.06pixels) with a maximum error of 3.7 mm (0.6 pixels). In 40 subjects undergoing pharmacological stress 201Tl myocardial SPET imaging, the mean cardiac axial creep movement was calculated as 3.1+/-0.7 mm (0. 49+/-0.11 pixels), with 13 out of 40 (32%) having a calculated motion of 1 pixel (6.3 mm) or more. The automatic image shift was visually judged to be within 1 pixel in all 160 image pair analyses, and the mean pixel value difference between image pairs was reduced following image shifting. It is concluded that multi-rotation 180 degrees SPET imaging provides raw data which allow objective and accurate motion detection of cardiac motion in thallium stress myocardial imaging, whilst the one-dimensional cross-correlation technique demonstrates adequate accuracy and reliability to be applied as an automatic motion screening technique on these data.

The opiate addiction test: a clinical evaluation of a quick test for physical dependence on opiate drugs.

1. Mydriasis (pupil dilation) in response to conjunctivally applied naloxone hydrochloride has been demonstrated using an innovative electronic binocular pupillometer in 40 opiate dependent patients, on maintenance methadone treatment. 2. No pupillary response to naloxone was seen when an identical procedure was carried out in a control population of 12 healthy volunteers. 3. After a baseline measurement of pupil size, two drops of naloxone hydrochloride were instilled into the conjunctival sac of one eye. Serial binocular pupillometry was then carried out at 5, 10, 15, 20, 25, 30, 35, 40 and 45 min post-instillation. 4. Discriminant analysis between the control and patient groups showed that the false negative rate (error of misclassification to the wrong population) was lowest (20%) at 40 min post-eyedrop instillation, with no false positives in the control group. 5. The study has therefore shown an improvement in the previously reported false negative rate (25%) [1,2], of the conjunctival naloxone test of opiate dependence, with the use of our innovative electronic binocular pupillometer.

Quantification of inflammatory bowel disease activity using technetium-99m HMPAO labelled leucocyte single photon emission computerised tomography (SPECT).

Technetium-99m HMPAO labelled white cell bowel uptake was quantified in 23 patients with suspected colitis by means of the novel technique of single photon emission computerised tomography (SPECT) using a standard gamma-camera. Uptake in colon segments was quantified on transaxial images and expressed as a fraction of marrow uptake (SPECT score). Segmental histological disease activity was assessed at colonoscopy (20) or at surgery (3). Segmental histology score correlated with SPECT score r = 0.79 (p < 0.001). Overall SPECT score for all affected segments correlated with Crohn's disease activity index (CDAI) r = 0.66, p = 0.001 and with laboratory activity indices; erythrocyte sedimentation rate r = 0.44, p = 0.03, C reactive protein r = 0.38, p = 0.05, and albumin r = -0.46, p = 0.03. Small bowel SPECT score in 13 patients correlated with CDAI r = 0.65, p < 0.01 but not with erythrocyte sedimentation rate or C reactive protein. Five patients with positive small bowel white cell uptake had normal C reactive protein and erythrocyte sedimentation rate. Overall SPECT score for disease at all sites correlated with both CDAI and with laboratory indices of inflammation. 99mTc HMPAO SPECT provides non-invasive and accurate quantification of inflammatory bowel disease activity in both large and small bowel and may be useful in the objective evaluation of treatment for inflammatory bowel disease.

A phantom and a procedure to obtain variable-object-contrast test images in gamma camera emission computed tomography (SPECT).

The value of test objects with a range of object contrast has been widely recognized for the testing of medical imaging equipment. A simple phantom is described, which, together with a data processing procedure, provides variable-contrast rod objects in gamma camera emission computed tomography (SPECT). There is only one compartment to fill with radioisotope, and data from hot rods, cold rods and a uniform section are available for analysis. The rod object contrast varies from 100% to 0%, with nine contrast steps used in this analysis. The measured image contrast in the transaxial slices is shown to be sensitive to variations in the system spatial resolution. With only one compartment to fill with radioisotope, this procedure is applicable for routine checking or optimization of gamma camera SPECT systems.

Kinetics of hepatic bile acid handling in cholestatic liver disease: effect of ursodeoxycholic acid.

BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA) is clinically beneficial in chronic cholestatic liver disease, but the underlying mechanisms are unclear. It has been suggested that intrahepatic retention of endogenous hydrophobic bile acids contributes to cholestasis and that the hydrophilic bile acid UDCA reduces this retention; the aim of our study was to test these hypotheses. METHODS: Twelve patients with primary biliary cirrhosis (PBC) and 5 with primary sclerosing cholangitis (PSC) were studied before and during UDCA (10 mg.kg-1.day-1) and compared with 11 healthy controls. Following intravenous 75Se labeled homocholic acid taurine (75SeHCAT) in the fasting state, abdominal gamma camera imaging was performed for 90 minutes. Initial hepatic uptake, transit time, net, and absolute excretory rates for 75SeHCAT were measured. RESULTS: Mean initial hepatic uptake was not different between patients and controls (17.2% and 19.9% dose/minute, not significant). However, net and absolute excretory rates were significantly reduced in patients (1.4% vs. 3.7% dose/minute, P < 0.0001; and 2.35% vs. 3.96% dose/minute, P < 0.02, respectively), and hepatic transit time was prolonged (18.7 minutes vs. 11.6 minutes, P < 0.002). UDCA improved net and absolute hepatic excretory rates and transit time (1.43% to 1.96% dose/minute, P < 0.001; 2.35% to 3.15% dose/minute, P < 0.005 and 18.7 to 14.7 minutes, P < 0.001, respectively). However, UDCA did not alter initial hepatic uptake. CONCLUSIONS: In PBC and PSC, there is a defect in hepatic bile acid excretion but not in uptake, implying bile acid retention. This retention is reduced by UDCA.

A general software package for the handling of medical images.

PICS (portable imaging computer software), is a software system designed for handling and processing a variety of types of medical image. It has been designed to satisfy the following criteria: (a) the software should be portable between different items of hardware with minimal alteration; (b) there should be a simple operator interface to enable use by inexperienced users, while avoiding the need for experienced users to be directed through tedious menu trees; (c) the programming environment should enable simple integration of new data handling protocols. To meet these requirements the software was written in FORTRAN using structured subroutine organization. The software has basic image handling and processing facilities and contains a comprehensive set of nuclear medicine clinical protocols. Other facilities include alignment of images from different modalities with display of superimposed images and ability to handle, analyse and display three-dimensional data sets. Data transfer programs have been written to capture data from gamma camera, CT, MRI, ultrasound and radiographs by converting the images to a common data format. The system provides a hospital with a central digital image handling resource, enabling investigation of the value of digital image processing in potential clinical applications.

A comparison of three indices of relative hepatic perfusion derived from dynamic liver scintigraphy.

Data from dynamic radiocolloid liver scintigraphy (DLS) have been analysed to calculate three indices of relative arterial to total hepatic perfusion. Ninety subjects have been studied, comprising 21 normals, 62 patients with metastatic liver disease and 7 patients with cirrhosis. Correlation coefficients above 0.81 were found in all patient groups between an index based on rates of liver uptake (the hepatic perfusion index, HPI) and a method based on quantitative liver uptake (the mesenteric fraction, MF). A further method employing the spleen to model arterial inflow (hepatic arterial ratio, HAR) had less agreement with both HPI and MF, with correlation coefficients below 0.76. Posterior images have previously been used to calculate HAR, and greater errors are expected in HAR from the anterior images acquired in this study. Receiver operating characteristic analysis showed that the diagnostic performance of HPI and MF indices in metastatic disease were not significantly different. For anterior image data analysis both HPI and MF were superior to HAR.

Regional indices of relative hepatic arterial perfusion from dynamic liver scintigraphy: the variability of indices and the use of parametric imaging.

Regional indices of relative arterial hepatic perfusion have been studied in 21 control subjects following dynamic radiocolloid scintigraphy of the liver (DLS). Three different indices have been calculated: the hepatic perfusion index (HPI); the hepatic arterial ratio (HAR) and the mesenteric fraction (MF). Three regions were defined in the upper, mid and lower right hepatic lobes and the three indices were calculated for each region. There was reasonable agreement between regional values of the same index with inter-regional correlation coefficients above 0.7 and standard errors in straight line fits of less than 0.093. There were significant regional differences for (1-MF) and HPI indices, but not for HAR. The index (1-MF) was calculated for each pixel and presented as a parametric image in 16 control subjects. The parametric images indicated the raised regional arterial indices due to overlying lung, right kidney and aorta. Parametric images may be of value to show the hepatic area free of significant overlying tissue and therefore available for analysis by DLS. However, the results suggest that the observed variability of single pixel indices limit the potential of parametric imaging for the localization of small focal lesions.

An association between parameters of liver blood flow and percentage hepatic replacement with tumour.

The extent of hepatic replacement with tumour is a significant prognostic factor in patients with liver metastases. Measuring the percentage hepatic replacement (PHR) accurately is difficult, but is important for both patient management and clinical trial evaluation. This study correlates haemodynamic indices obtained by dynamic liver scintigraphy (DLS) with estimates of PHR made from isotope scan, ultrasound, CT scan and laparotomy in 45 patients with established colorectal liver metastases and 21 controls who also underwent DLS. There was a significant reduction in the mesenteric fraction (MF) in the group of patients with metastases compared to the controls (P less than 0.001), and also a significant trend for progressive reduction in the MF with increasing PHR. A significant rise in an index of total hepatic arterial blood flow was also demonstrated with increasing PHR. These results are important with current interest in regional hepatic arterial therapy, and may prove of clinical value for prediction or monitoring of response to therapy.