Comparison of 99mTc ciprofloxacin, 99mTc white blood cell and three-phase bone imaging in the diagnosis of hip prosthesis infections: improved diagnostic accuracy with extended imaging time.

The purpose of this study was to compare the utility of 99mTc labelled ciprofloxacin (Infecton) imaging with the 99mTc white blood cell and three-phase bone imaging procedures for identifying hip prosthesis infection. We studied 30 symptomatic patients in whom infection was confirmed in eight and excluded in 22 cases based on clinical and microbiological findings. 99mTc ciprofloxacin images were obtained at 1, 4 and 24 h after the injection of the tracer, and the data were compared to those obtained from 99mTc leukocyte and three-phase bone imaging. The 99mTc ciprofloxacin imaging correctly identified all true infections. In 13 (59%) of the non-infected patients, non-specific uptake of 99mTc ciprofloxacin was found in the 1-h and 4-h images, which disappeared, however, in the 24-h images. When the early and late 99mTc ciprofloxacin images were compared, the specificity was found to improve from 41% to 95%, positive predictive value from 38% to 89%, and the diagnostic accuracy from 57% to 97%. The accuracy of the conventional 99mTc leukocyte imaging was 90%. Dynamic bone imaging also yielded abnormal findings in all the infected patients although also in 23% of the non-infected patients. Current data indicate that 99mTc ciprofloxacin is a useful method for confirming hip prosthesis infection. The diagnostic efficiency of this method is improved when the imaging time is extended to 24 h post-injection of the tracer.

99m Tc-ciprofloxacin (Infecton) imaging in the diagnosis of knee prosthesis infections.

The purpose of this study was to evaluate the usefulness of 99mTc labelled ciprofloxacin imaging in detecting the presence of infection in patients with symptomatic knee prostheses. Among 16 randomly selected patients of whom seven had infection based on clinical and microbiological findings and nine did not, 99mTc-ciprofloxacin images were obtained at 1, 4 and 24h after the injection of the tracer. While there was some diffuse non-specific accumulation of 99mTc-ciprofloxacin in large synovial joints and in prosthetic knee joints, the infected knee prostheses were found to show more intensive focal uptake, which also extended outside the synovial cavity. The infection related uptake remained visible in the 24h images, whereas non-specific uptake had a fading tendency at this time point. 99mTc-ciprofloxacin imaging showed diagnostic sensitivity of 86% and a specificity of 78% for correctly classifying the presence of infection. The data indicate that 99mTc-ciprofloxacin imaging may be used in the diagnosis of knee prosthesis infections. Infection-related uptake remains visible in the 24h images and is typically found also outside the synovial cavity, which should be noted in the evaluation of the images.

Improved method for detecting knee replacement infections based on extended combined 99mTc-white blood cell/bone imaging.

The purpose of this study was to evaluate whether an extension of the imaging time to 24 h post-injection improves the diagnostic accuracy of technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) leucocyte imaging in detecting knee replacement infections. Thirty patients were studied, with infection confirmed in eight (27%) and excluded in 22 on the basis of clinical and microbiological findings. Leucocyte imaging was carried out at 2-4 h (routine images) and at 24 h (late images) post-injection. For comparison, bone imaging with technetium-99m-hydroxydiphosphonate (99mTc-HDP) was carried out at arterial, soft tissue and metabolic phases. Late leucocyte imaging was found to be more sensitive (100% vs. 87.5%) and more specific (82% vs. 77%) than routine leucocyte imaging in detecting infections. All the bone imaging methods showed a sensitivity of 100%, whereas the specificity varied from only 5% to 23%. All procedures had high negative predictive values (NPVs) (94 to 100%) for excluding infection. However, the positive predictive value (PPV) was only 28 to 32% for bone imaging and 58% for routine leucocyte imaging, whereas late leucocyte imaging showed a PPV of 67% and a diagnostic accuracy of 87%. The data indicate that late leucocyte imaging may be superior to routine leucocyte imaging for examining patients with symptomatic knee replacements.

Quality of dynamic radionuclide renal imaging: multicentre evaluation using a functional renal phantom.

The aim of this study was to evaluate the quality of dynamic radionuclide renal imaging in Finland. Nineteen nuclear medicine departments participated. A functional renal phantom was imaged and interpreted as a patient-like study. Reconstruction and printouts were performed according to the clinical routine of each laboratory. Three nuclear medicine specialists anonymously evaluated the quality of the image sets. The visual scores of the experts were ranked from one to five. In addition, several numerical time-activity parameters were calculated and compared between the laboratories. The average visual scores of the experts for the image sets were 3.2+/-0.5 (range 2.4-4.2). Only two laboratories received a score value of 4 or higher. The average error for the time to reach maximum activity (T(max)) ranged from -29 to +18% and for the washout time to reach half activity from maximum activity (T(1/2)) ranged from -43 to +66%. These results suggest that the difference in calculated parameters between laboratories is most probably due to variations in study protocols and analysis programmes. The need for external quality assurance and quality improvement in nuclear renal imaging is evident and is recommended for regular use.

Extended combined 99mTc-white blood cell and bone imaging improves the diagnostic accuracy in the detection of hip replacement infections.

Although the diagnosis of hip prosthesis infection is clinically important, X-ray studies, blood chemistry and synovial fluid aspiration may be unreliable for this purpose. The aim of this study was to evaluate whether extending the time for technetium-99m labelled leucocyte imaging to 24 h post injection improves the accuracy of diagnosis of hip replacement infections. We studied 64 symptomatic patients with hip prostheses. The presence of infections was verified by intraoperative bacterial cultures, and infection was excluded either by negative operative findings or by follow-up for at least 1 year. Leucocyte imaging was done with 99mTc-hexamethylpropylene amine oxime (HMPAO)-labelled leucocytes at 2-4 h (routine images) and at 24 h (late images) after the injection of the leucocytes. In addition, bone imaging was carried out with 99mTc-hydroxydiphosphonate (HDP) at the arterial, soft tissue and metabolic phases. A standardised method was used to compare leucocyte images with bone metabolic images. In this material, there were six confirmed infections. All the bone imaging methods had a sensitivity of 100% in detecting prosthesis infections whereas the specificity varied from only 2% to 82%. Routine leucocyte imaging was less sensitive (50% vs 83%) and less specific (90% vs 100%) than late leucocyte imaging. All tests had a high negative predictive value for excluding infection (95%-100%). However, both bone (10%-38%) and routine leucocyte imaging (33%) showed a poor positive predictive value (PPV), whereas late leucocyte imaging had a PPV of 100% and a diagnostic accuracy of 98%. We conclude that late leucocyte imaging improves the specificity of diagnosis of infected hip prostheses. This type of imaging procedure should be combined with three-phase bone scintigraphy in studies of patients with painful joint replacement.

Toward a quantum-mechanical description of metal-assisted phosphoryl transfer in pyrophosphatase.

The wealth of kinetic and structural information makes inorganic pyrophosphatases (PPases) a good model system to study the details of enzymatic phosphoryl transfer. The enzyme accelerates metal-complexed phosphoryl transfer 10(10)-fold: but how? Our structures of the yeast PPase product complex at 1.15 A and fluoride-inhibited complex at 1.9 A visualize the active site in three different states: substrate-bound, immediate product bound, and relaxed product bound. These span the steps around chemical catalysis and provide strong evidence that a water molecule (O(nu)) directly attacks PPi with a pK(a) vastly lowered by coordination to two metal ions and D117. They also suggest that a low-barrier hydrogen bond (LBHB) forms between D117 and O(nu), in part because of steric crowding by W100 and N116. Direct visualization of the double bonds on the phosphates appears possible. The flexible side chains at the top of the active site absorb the motion involved in the reaction, which may help accelerate catalysis. Relaxation of the product allows a new nucleophile to be generated and creates symmetry in the elementary catalytic steps on the enzyme. We are thus moving closer to understanding phosphoryl transfer in PPases at the quantum mechanical level. Ultra-high resolution structures can thus tease out overlapping complexes and so are as relevant to discussion of enzyme mechanism as structures produced by time-resolved crystallography.

Brain perfusion after treatment of childhood acute lymphoblastic leukemia.

UNLABELLED: Children with acute lymphoblastic leukemia (ALL) have impairment in their neuropsychological functioning and morphological changes in their brain after cranial irradiation and chemotherapy. The aim of this study was to identify possible brain perfusion defects caused by different types of treatment and their association with abnormalities in cerebral MRI and neuropsychological and clinical neurological findings. METHODS: Twenty-five consecutive children with ALL at the cessation of chemotherapy or after 1 yr were included. All of the children were given intravenous and intrathecal methotrexate for central nervous system therapy, 13 of them received cranial radiation therapy. Brain SPECT, cerebral MRI, clinical neurological and neuropsychological evaluations were performed. RESULTS: Eleven of the 25 patients (44%) had brain perfusion defects in SPECT, eight of whom were treated with chemotherapy alone, and three received cranial irradiation. Two patients had small bilateral white matter changes on MRI; their brain SPECT scans were abnormal, although the findings were not related. Impairment of neuropsychological functioning was found in 86% of the patients tested. No significant difference between the patients with abnormal and normal SPECT were found. Those patients with abnormal SPECT were younger than those with normal SPECT and had received more frequent intravenous methotrexate infusions. CONCLUSION: Brain SPECT detected perfusion defects that had occurred after treatment for childhood ALL. These defects may be related to frequent administration of a combination of intravenous and intrathecal methotrexate and/or young age.