Mechanistic Studies on the Self-Assembly of PLGA Patchy Particles and Their Potential Applications in Biomedical Imaging.

Currently, several challenges prevent poly(lactic-co-glycolic acid) (PLGA) particles from reaching clinical settings. Among these is a lack of understanding of the molecular mechanisms involved in the formation of these particles. We have been studying in depth the formation of patchy polymeric particles. These particles are made of PLGA and lipid-polymer functional groups. They have unique patch-core-shell structural features: hollow or solid hydrophobic cores and a patchy surface. Previously, we identified the shear stress as the most important parameter in a patchy particle's formation. Here, we investigated in detail the role of shear stress in the patchy particle's internal and external structure using an integrative experimental and computational approach. By cross-sectioning the multipatch particles, we found lipid-based structures embedded in the entire PLGA matrix, which represents a unique finding in the PLGA field. By developing novel computational fluid dynamics and molecular dynamics simulations, we found that the shear stress determines the internal structure of the patchy particles. Equally important, we discovered that these particles emit a photoacoustic (PA) signal in the optical clinical imaging window. Our results show that particles with multiple patches emit a higher PA signal than single-patch particles. This phenomenon most likely is due to the fact that multipatchy particles absorb more heat than single-patchy particles as shown by differential scanning calorimetry analysis. Furthermore, we demonstrated the use of patchy polymeric particles as photoacoustic molecular probes both in vitro and in vivo studies. The fundamental studies described here will help us to design more effective PLGA carriers for a number of medical applications as well as to accelerate their medical translation.

Identification of Small, Regularly Shaped Cerebral Aneurysms Prone to Rupture.

BACKGROUND AND PURPOSE: Many small, regularly shaped cerebral aneurysms rupture; however, they usually receive a low score based on current risk-assessment methods. Our goal was to identify patient and aneurysm characteristics associated with rupture of small, regularly shaped aneurysms and to develop and validate predictive models of rupture in this aneurysm subpopulation. MATERIALS AND METHODS: Cross-sectional data from 1079 aneurysms smaller than 7 mm with regular shapes (without blebs) were used to train predictive models for aneurysm rupture using machine learning methods. These models were based on the patient population, aneurysm location, and hemodynamic and geometric characteristics derived from image-based computational fluid dynamics models. An independent data set with 102 small, regularly shaped aneurysms was used for validation. RESULTS: Adverse hemodynamic environments characterized by strong, concentrated inflow jets, high speed, complex and unstable flow patterns, and concentrated, oscillatory, and heterogeneous wall shear stress patterns were associated with rupture in small, regularly shaped aneurysms. Additionally, ruptured aneurysms were larger and more elongated than unruptured aneurysms in this subset. A total of 5 hemodynamic and 6 geometric parameters along with aneurysm location, multiplicity, and morphology, were used as predictive variables. The best machine learning rupture prediction-model achieved a good performance with an area under the curve of 0.84 on the external validation data set. CONCLUSIONS: This study demonstrated the potential of using predictive machine learning models based on aneurysm-specific hemodynamic, geometric, and anatomic characteristics for identifying small, regularly shaped aneurysms prone to rupture.

Evaluation of Outcome Prediction of Flow Diversion for Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Identifying and predicting which aneurysms are likely to quickly occlude and which ones are likely to remain open following treatment with flow-diverting devices is important to develop optimal patient management strategies. The purpose of this study was to evaluate predictions based on computational fluid dynamics models using the elastase rabbit aneurysm model. MATERIALS AND METHODS: A series of 13 aneurysms created in rabbits were treated with flow diverters, and outcomes were angiographically assessed at 8 weeks' follow-up. Computational fluid dynamics models were constructed from pretreatment 3D rotational angiograms and Doppler ultrasound flow velocity measurements. Postimplantation mean aneurysm inflow rate and flow velocity were used to prospectively predict aneurysm occlusion blinded to the actual outcomes. Specifically, if both variables were below their corresponding thresholds, fast occlusion was predicted, while if one of them was above the threshold, slow or incomplete occlusion was predicted. RESULTS: Of the 13 aneurysms included, 8 were incompletely occluded 8 weeks after treatment, and 5 were completely occluded. A total of 10 computational fluid dynamics-based predictions agreed with the angiographic outcome, reaching 77% accuracy, 80% sensitivity, and 75% specificity. Posttreatment mean velocity alone was able to achieve the same predictive power as the combination of inflow rate and velocity. CONCLUSIONS: Subject-specific computational fluid dynamics models of the hemodynamic conditions created immediately after implantation of flow-diverting devices in experimental aneurysms created in rabbits are capable of prospectively predicting, with a reasonable accuracy, which aneurysms will completely occlude and which ones will remain incompletely occluded.

Regional Aneurysm Wall Enhancement is Affected by Local Hemodynamics: A 7T MRI Study.

BACKGROUND AND PURPOSE: Aneurysm wall enhancement has been proposed as a biomarker for inflammation and instability. However, the mechanisms of aneurysm wall enhancement remain unclear. We used 7T MR imaging to determine the effect of flow in different regions of the wall. MATERIALS AND METHODS: Twenty-three intracranial aneurysms imaged with 7T MR imaging and 3D angiography were studied with computational fluid dynamics. Local flow conditions were compared between aneurysm wall enhancement and nonenhanced regions. Aneurysm wall enhancement regions were subdivided according to their location on the aneurysm and relative to the inflow and were further compared. RESULTS: On average, wall shear stress was lower in enhanced than in nonenhanced regions (P = .05). Aneurysm wall enhancement regions at the neck had higher wall shear stress gradients (P = .05) with lower oscillations (P = .05) than nonenhanced regions. In contrast, aneurysm wall enhancement regions at the aneurysm body had lower wall shear stress (P = .01) and wall shear stress gradients (P = .008) than nonenhanced regions. Aneurysm wall enhancement regions far from the inflow had lower wall shear stress (P = .006) than nonenhanced regions, while aneurysm wall enhancement regions close to the inflow tended to have higher wall shear stress than the nonenhanced regions, but this association was not significant. CONCLUSIONS: Aneurysm wall enhancement regions tend to have lower wall shear stress than nonenhanced regions of the same aneurysm. Moreover, the association between flow conditions and aneurysm wall enhancement seems to depend on the location of the region on the aneurysm sac. Regions at the neck and close to the inflow tend to be exposed to higher wall shear stress and wall shear stress gradients. Regions at the body, dome, or far from the inflow tend to be exposed to uniformly low wall shear stress and have more aneurysm wall enhancement.

Quantitative bone SPECT analysis of mandibular condyles in an asymptomatic population: an approach to normal reference values.

Bone scintigraphy is an extremely valuable technique in diagnosis and treatment planning for patients with condylar hyperplasia (CH). The main objective of this study was to develop an approach to determine normal activity values in the mandibular condyles, adjusted to age and sex, through quantitative analysis of bone single-photon emission computed tomography (SPECT) on a condyle-by-condyle basis and to compare these values with those of a control group comprising patients with confirmed CH. Technetium 99 m-methylene diphosphonate (99mTc-MDP) SPECT studies of the mandibular condyles were performed in patients with no mandibular pathology for quantitative analysis. Regions of interest were drawn on slices representing the upper, middle, and inferior thirds of each condyle and on the summation of transaxial slices representing the whole condyle (three-dimensional approach). The clivus was used for internal validation and the condyle to clivus ratios were calculated. These ratios were compared between 'normal' and 'diseased' condyles. A total 144 condyles in normal patients and 25 in confirmed CH patients were analysed. Differences between the ratios were evaluated through the coefficient of variation. In normal patients, the ratios to the clivus on the summed condyle image showed the lowest variability: range 0.3-1.28 (median 0.74). The quantile regression model showed significant differences with respect to sex, but not to age. The Mann-Whitney test showed significant differences in the ratios to clivus between normal and diseased condyles (P<0.0001).

Analysis of Flow Dynamics and Outcomes of Cerebral Aneurysms Treated with Intrasaccular Flow-Diverting Devices.

BACKGROUND AND PURPOSE: Intrasaccular flow diversion offers a promising treatment option for complex bifurcation aneurysms. The purpose of this study was to compare the flow conditions between successfully occluded and incompletely occluded aneurysms treated with intrasaccular devices. MATERIALS AND METHODS: The hemodynamics in 18 completely occluded aneurysms after treatment with intrasaccular devices was compared against 18 that were incompletely occluded at follow-up. Hemodynamic and geometric parameters were obtained from computational fluid dynamics models constructed from 3D angiographies. Models of the intrasaccular devices were created and interactively deployed within the vascular models using posttreatment angiography images for guidance. Hemodynamic and geometric variables were compared using the Mann-Whitney test and univariate logistic regression analysis. RESULTS: Incomplete occlusion was associated with large posttreatment mean aneurysm inflows (P = .02) and small reductions in the mean inflow rate (P = .01) and inflow concentration index (P = .03). Incompletely occluded aneurysms were larger (P = .002) and had wider necks (P = .004) than completely occluded aneurysms and tended to have more complex flow patterns, though this trend was not significant after adjusting for multiple testing. CONCLUSIONS: The outcome of cerebral aneurysm treatment with intrasaccular flow diverters is associated with flow conditions created immediately after device implantation. Flow conditions unfavorable for immediate and complete occlusion seem to be created by improper positioning or orientation of the device. Complete occlusion is more difficult to achieve in larger aneurysms, aneurysms with wider necks, and aneurysms with stronger and more complex flows.

Reproducibility of haemodynamical simulations in a subject-specific stented aneurysm model--a report on the Virtual Intracranial Stenting Challenge 2007.

This paper presents the results of the Virtual Intracranial Stenting Challenge (VISC) 2007, an international initiative whose aim was to establish the reproducibility of state-of-the-art haemodynamical simulation techniques in subject-specific stented models of intracranial aneurysms (IAs). IAs are pathological dilatations of the cerebral artery walls, which are associated with high mortality and morbidity rates due to subarachnoid haemorrhage following rupture. The deployment of a stent as flow diverter has recently been indicated as a promising treatment option, which has the potential to protect the aneurysm by reducing the action of haemodynamical forces and facilitating aneurysm thrombosis. The direct assessment of changes in aneurysm haemodynamics after stent deployment is hampered by limitations in existing imaging techniques and currently requires resorting to numerical simulations. Numerical simulations also have the potential to assist in the personalized selection of an optimal stent design prior to intervention. However, from the current literature it is difficult to assess the level of technological advancement and the reproducibility of haemodynamical predictions in stented patient-specific models. The VISC 2007 initiative engaged in the development of a multicentre-controlled benchmark to analyse differences induced by diverse grid generation and computational fluid dynamics (CFD) technologies. The challenge also represented an opportunity to provide a survey of available technologies currently adopted by international teams from both academic and industrial institutions for constructing computational models of stented aneurysms. The results demonstrate the ability of current strategies in consistently quantifying the performance of three commercial intracranial stents, and contribute to reinforce the confidence in haemodynamical simulation, thus taking a step forward towards the introduction of simulation tools to support diagnostics and interventional planning.

Appropriate use of noninvasive ischemia testing to guide revascularization decision making following acute ST elevation myocardial infarction in Latin American countries: Results from an expert panel meeting of the International Atomic Energy Agency. / Uso adecuado de las pruebas no invasivas de isquemia para guiar la toma de decisión sobre revascularización tras un infarto agudo de miocardio con elevación del segmento ST en países iberoamericanos: Resultados de la reunión de un panel de expertos de la International Atomic Energy Agency.

Across Latin American and Caribbean countries, cardiovascular disease and especially ischemic heart disease is currently the main cause of death both in men and in women. For most Latin American and Caribbean countries, public and community health efforts aim to define care strategies which are both clinically and cost effective and promote primary and secondary prevention, resulting in improved patient outcomes. The optimal approach to deal with acute events such as ST-elevation myocardial infarction (STEMI) is a matter of controversy; however, there is an expanding role for assessing residual ischemic burden in STEMI patients following primary percutaneous coronary intervention. Although randomized clinical trials have established the value of staged fractional flow reserve-guided revascularization, the use of noninvasive functional imaging modalities may play a similar role at a much lower cost. For LAC, available stress imaging techniques could be applied to define residual ischemia in the non-infarct related artery and to target revascularization in a staged procedure after primary percutaneous coronary intervention The use of nuclear cardiac imaging, supported by its relatively wide availability, moderate cost, and robust quantitative capabilities, may serve to guide effective care and to reduce subsequent cardiac events in patients with coronary artery disease. This noninvasive approach may avert potential safety issues with repeat and lengthy invasive procedures, and serve as a baseline for subsequent follow-up stress testing following the index STEMI event. This consensus document was devised from an expert panel meeting of the International Atomic Energy Agency, highlighting available evidence with a focus on the utility of stress myocardial perfusion imaging in post-STEMI patients. The document could serve as guidance to the prudent and appropriate use of nuclear imaging for targeting therapeutic management and avoiding unnecessary invasive procedures within Latin American and Caribbean countries, where resources could be scarce.

Identification of Hostile Hemodynamics and Geometries of Cerebral Aneurysms: A Case-Control Study.

BACKGROUND AND PURPOSE: Hostile hemodynamic conditions and geometries are thought to predispose aneurysms for instability and rupture. This study compares stable, unstable, and ruptured aneurysms while controlling for location and patient characteristics. MATERIALS AND METHODS: The hemodynamics and geometries of 165 stable, 65 unstable, and 554 ruptured aneurysms were compared. Hemodynamics was modeled using image-based computational fluid dynamics. Case-control pairs were selected matching aneurysm location, patient age, and sex. Paired Wilcoxon tests were used to compare hemodynamic and geometric variables among different aneurysm groups. The pairing was repeated 100 times, and the combined P values were calculated and adjusted for multiple testing. RESULTS: Ruptured aneurysms had lower minimum wall shear stress (P = .03), higher maximum wall shear stress (P = .03), more concentrated (P = .03) and mean oscillatory shear stress (P = .03), higher maximum velocity (P = .03), and more complex flows (vortex core-line length, P = .03) than stable aneurysms. Similarly, unstable aneurysms had more concentrated shear stress (P = .04) and more complex flows (vortex core-line length, P = .04) than stable aneurysms. Compared with stable aneurysms, ruptured aneurysms were larger (size ratio, aneurysm size/vessel size, P = .03), more elongated (aspect ratio, P = .03), and irregular (nonsphericity index, P = .03). Similarly, unstable aneurysms were larger (size ratio, P = .04), more elongated (aspect ratio, P = .04), and irregular (bulge location, P = .04; area-weighted Gaussian curvature; P = .04) than stable aneurysms. No significant differences were found between unstable and ruptured aneurysms. CONCLUSIONS: Unstable and ruptured aneurysms have more complex flows with concentrated wall shear stress and are larger, more elongated, and irregular than stable aneurysms, independent of aneurysm location and patient sex and age.

Understanding Angiography-Based Aneurysm Flow Fields through Comparison with Computational Fluid Dynamics.

BACKGROUND AND PURPOSE: Hemodynamics is thought to be an important factor for aneurysm progression and rupture. Our aim was to evaluate whether flow fields reconstructed from dynamic angiography data can be used to realistically represent the main flow structures in intracranial aneurysms. MATERIALS AND METHODS: DSA-based flow reconstructions, obtained during interventional treatment, were compared qualitatively with flow fields obtained from patient-specific computational fluid dynamics models and quantitatively with projections of the computational fluid dynamics fields (by computing a directional similarity of the vector fields) in 15 cerebral aneurysms. RESULTS: The average similarity between the DSA and the projected computational fluid dynamics flow fields was 78% in the parent artery, while it was only 30% in the aneurysm region. Qualitatively, both the DSA and projected computational fluid dynamics flow fields captured the location of the inflow jet, the main vortex structure, the intrasaccular flow split, and the main rotation direction in approximately 60% of the cases. CONCLUSIONS: Several factors affect the reconstruction of 2D flow fields from dynamic angiography sequences. The most important factors are the 3-dimensionality of the intrasaccular flow patterns and inflow jets, the alignment of the main vortex structure with the line of sight, the overlapping of surrounding vessels, and possibly frame rate undersampling. Flow visualization with DSA from >1 projection is required for understanding of the 3D intrasaccular flow patterns. Although these DSA-based flow quantification techniques do not capture swirling or secondary flows in the parent artery, they still provide a good representation of the mean axial flow and the corresponding flow rate.

Flow Conditions in the Intracranial Aneurysm Lumen Are Associated with Inflammation and Degenerative Changes of the Aneurysm Wall.

BACKGROUND AND PURPOSE: Saccular intracranial aneurysm is a common disease that may cause devastating intracranial hemorrhage. Hemodynamics, wall remodeling, and wall inflammation have been associated with saccular intracranial aneurysm rupture. We investigated how saccular intracranial aneurysm hemodynamics is associated with wall remodeling and inflammation of the saccular intracranial aneurysm wall. MATERIALS AND METHODS: Tissue samples resected during a saccular intracranial aneurysm operation (11 unruptured, 9 ruptured) were studied with histology and immunohistochemistry. Patient-specific computational models of hemodynamics were created from preoperative CT angiographies. RESULTS: More stable and less complex flows were associated with thick, hyperplastic saccular intracranial aneurysm walls, while slower flows with more diffuse inflow were associated with degenerated and decellularized saccular intracranial aneurysm walls. Wall degeneration (P = .041) and rupture were associated with increased inflammation (CD45+, P = .031). High wall shear stress (P = .018), higher vorticity (P = .046), higher viscous dissipation (P = .046), and high shear rate (P = .046) were associated with increased inflammation. Inflammation was also associated with lack of an intact endothelium (P = .034) and the presence of organized luminal thrombosis (P = .018), though overall organized thrombosis was associated with low minimum wall shear stress (P = .034) and not with the flow conditions associated with inflammation. CONCLUSIONS: Flow conditions in the saccular intracranial aneurysm are associated with wall remodeling. Inflammation, which is associated with degenerative wall remodeling and rupture, is related to high flow activity, including elevated wall shear stress. Endothelial injury may be a mechanism by which flow induces inflammation in the saccular intracranial aneurysm wall. Hemodynamic simulations might prove useful in identifying saccular intracranial aneurysms at risk of developing inflammation, a potential biomarker for rupture.

Hemodynamic Characteristics of Ruptured and Unruptured Multiple Aneurysms at Mirror and Ipsilateral Locations.

BACKGROUND AND PURPOSE: Different hemodynamic patterns have been associated with aneurysm rupture. The objective was to test whether hemodynamic characteristics of the ruptured aneurysm in patients with multiple aneurysms were different from those in unruptured aneurysms in the same patient. MATERIALS AND METHODS: Twenty-four mirror and 58 ipsilateral multiple aneurysms with 1 ruptured and the others unruptured were studied. Computational fluid dynamics models were created from 3D angiographies. Case-control studies of mirror and ipsilateral aneurysms were performed with paired Wilcoxon tests. RESULTS: In mirror pairs, the ruptured aneurysm had more oscillatory wall shear stress (P = .007) than the unruptured one and tended to be more elongated (higher aspect ratio), though this trend achieved only marginal significance (P = .03, 1-sided test). In ipsilateral aneurysms, ruptured aneurysms had larger maximum wall shear (P = .05), more concentrated (P < .001) and oscillatory wall shear stress (P < .001), stronger (P < .001) and more concentrated inflow jets (P < .001), larger maximum velocity (P < .001), and more complex flow patterns (P < .001) compared with unruptured aneurysms. Additionally, ruptured aneurysms were larger (P < .001) and more elongated (P < .001) and had wider necks (P < .001) and lower minimum wall shear stress (P < .001) than unruptured aneurysms. CONCLUSIONS: High wall shear stress oscillations and larger aspect ratios are associated with rupture in mirror aneurysms. Adverse flow conditions characterized by high and concentrated inflow jets; high, concentrated, and oscillatory wall shear stress; and strong, complex and unstable flow patterns are associated with rupture in ipsilateral multiple aneurysms. In multiple ipsilateral aneurysms, these unfavorable flow conditions are more likely to develop in larger, more elongated, more wide-necked, and more distal aneurysms.

Angioarchitectures and Hemodynamic Characteristics of Posterior Communicating Artery Aneurysms and Their Association with Rupture Status.

BACKGROUND AND PURPOSE: Intracranial aneurysms originating at the posterior communicating artery are known to have high rupture risk compared with other locations. We tested the hypothesis that different angioarchitectures (ie, branch point configuration) of posterior communicating artery aneurysms are associated with aneurysm hemodynamics, which in turn predisposes aneurysms to rupture. MATERIALS AND METHODS: A total of 313 posterior communicating artery aneurysms (145 ruptured, 168 unruptured) were studied with image-based computational fluid dynamics. Aneurysms were classified into different angioarchitecture types depending on the location of the aneurysm with respect to parent artery bifurcation. Hemodynamic characteristics were compared between ruptured and unruptured aneurysms, as well as among aneurysms with different angioarchitectures. RESULTS: Angioarchitecture was associated with rupture (P = .003). Ruptured aneurysms had higher, more concentrated, and more oscillatory wall shear stress distributions (maximum wall shear stress, P < .001; shear concentration index, P < .001; mean oscillatory shear index, P < .001), stronger and more concentrated inflow jets (represented as Q, P = .01; inflow concentration index, P < .001), and more complex and unstable flow patterns (vortex core length, P < .001; proper orthogonal decomposition entropy, P < .001) compared with unruptured aneurysms. These adverse conditions were more common in aneurysms with bifurcation-type angioarchitectures compared with those with lateral or sidewall angioarchitectures. Interestingly, ruptured aneurysms also had lower normalized mean wall shear stress (P = .02) and minimum wall shear stress (P = .002) than unruptured aneurysms. CONCLUSIONS: High-flow intrasaccular hemodynamic characteristics, commonly found in bifurcation-type angioarchitectures, are associated with the posterior communicating artery aneurysm rupture status. These characteristics include strong and concentrated inflow jets, concentrated regions of elevated wall shear stress, oscillatory wall shear stress, lower normalized wall shear stress, and complex and unstable flow patterns.

Optimum processing protocols for volume determination of the liver and spleen from SPECT imaging with technetium-99m sulfur colloid.

A study of the effects of processing parameters on the determination of liver and spleen volume from SPECT data was performed. A method for volume determination using a threshold algorithm was calibrated against phantoms and applied to 60 patient studies. Good reproducibility was found using different projections and computing the volume on separate days. Variations of the measured volumes with the threshold value, reconstruction filter cutoff frequency and attenuation correction were investigated. Reconstruction parameters producing best image quality were also determined. A threshold of 25% of the maximum value in the organ was determined from phantom studies. Changes of 1% around this value yielded changes of 2-3% in the computed volume. No significant change was noted as cutoff frequencies varied between 0.4 and 0.85 of Nyquist (0.031 to 0.066 cycles/cm) for a third order Butterworth filter. Attenuation correction produced a decrease of 9% and 6% in liver and spleen measured volume respectively. Best image quality was obtained with 0.4 Nyquist (0.031 cycles/cm) cutoff frequency for third order Butterworth filter and attenuation correction. It is concluded that optimal parameters must be determined for any processing protocol, and must then be adhered to in future applications to insure clinical accuracy, especially those parameters demonstrating the most quantitative and qualitative sensitivity.

Human pharmacokinetics and radiopharmacological studies of the myocardial perfusion agent: technetium (2-carbomethoxy-2-isocyano-propane)6+.

The myocardial perfusion agent technetium (2-carbomethoxy-2-isocyano-propane)6+ (99mTc-CPI) is unique from other cationic technetium isonitrile complexes in that it exhibits moderate washout from the heart and rapid hepatobiliary clearance in animal models and human volunteers. Dynamic imaging and HPLC analysis were performed in humans and guinea pigs to outline the pharmacological basis of its pharmacokinetics. Enzymatic hydrolysis of the terminal ester groups in blood was found to occur at a moderate rate producing new species that have been shown not to accumulate in heart tissue. However, after extraction by the heart, liver or kidneys, the 99mTc-CPI complex undergoes metabolism at a much slower rate than observed in the blood. Differences in hydrolysis rate and products obtained indicate separate mechanisms of hydrolysis occurring in blood and other organs. It is proposed that the heart washout occurring after hydrolysis produces a neutral compound which is no longer retained by the negative cytosolic and mitochondrial membrane potentials in myocardial tissue.

Detection of recurrent malignant melanoma with 99mTc-MIBI scintigraphy.

Initial reports suggest that 99mTc-methoxyisobutylisonitrile (MIBI) scanning may be of clinical value in staging patients with malignant melanoma. We carried out a study to evaluate the potential of this technique in the detection of recurrent disease. Whole-body 99mTC-MIBI scans were performed in 81 patients with a history of a surgically excised MM: 28 with known recurrent lesions and 53 during follow-up without evidence of disease. Images started 10 min post-injection, using a dose of 740 MBq. Diagnoses were confirmed by cytological/histological examination or at least one conventional imaging modality. Blinded interpretations of the MIBI scans were performed. Whole-body MIBI scanning correctly detected 68 (92%) of 74 metastatic lesions in the following sites: regional lymph nodes (n=23), non-regional lymph nodes (n=10), skin (n=16), brain/cerebellum (n=6), lung (n=8), bone (n=4) and breast (n=1). The technique failed to detect three subcutaneous regressive lesions (< 1 cm), one liver metastasis, one spleen metastasis and a case of multiple small lesions of the duodenal mucous membrane. In 14 patients the procedure detected previously unknown metastatic lesions. These results suggest that 99mTc-MIBI scanning is an effective imaging modality for whole-body screening of metastatic disease in malignant melanoma patients with the potential to influence treatment planning.

99Tc(m)-MIBI scanning of the thyroid gland in patients with markedly decreased pertechnetate uptake.

Diffusely reduced 99Tc(m)-pertechnetate uptake is a relatively infrequent but annoying finding that impairs evaluation of the thyroid gland. We studied 32 female patients aged 19-85 years with markedly reduced pertechnetate uptake. The following causes of reduced pertechnetate uptake were recognized: treatment with iodinated pharmaceuticals (n = 15), suppression therapy with T4 (n = 11), subacute thyroiditis (n = 5) and massive tumour replacement (n = 1). 99Tc(m)-MIBI thyroid scintigraphy was performed within 24 h of the pertechnetate study. The results were correlated with neck ultrasound, serum TSH (n = 25) and surgical findings in patients who had been operated on. The technique identified the following conditions: normally sized thyroids (n = 4), diffuse goitres (n = 8), multinodular goitres (n = 17) and solitary thyroid nodules (n = 3). Moreover, substernal goitres were identified in nine patients. This condition was confirmed at surgery in seven patients. Ultrasonography was concordant in 29 of 32 patients in terms of thyroid size and structure, but failed to demonstrate substernal thyroid tissue. Our results suggest that 99Tc(m)-MIBI scintigraphy may contribute to the diagnosis of thyroid pathology and treatment planning in patients with diffusely decreased 99Tc(m)-pertechnetate uptake.

Changes in the cerebral blood flow in postlingual cochlear implant users.

Five postlingually deaf patients (age range 28-58 years) with multichannel cochlear implants were examined with single photon emission tomography (SPECT) (triple-head rotating gamma camera). Changes in the regional cerebral blood flow (rCBF) after intravenous administration of technetium-99m ethyl cysteinate dimer (Tc-99m ECD) were assessed through a stimulation paradigm, consisting of: i) click stimuli (75 dB SPL) in the ear that was to be implanted, 2 weeks before surgery; ii) stimulation with the same click, one month after initial fitting; iii) stimulation with hearing sequential Spanish sentences one month after initial fitting. The results showed a significant increase in the rCBF in the primary left auditory area and in the right auditory cortex, in conditions ii) and iii). The rCBF also showed a significant asymmetrical increase in the frontal lobes when the patient was hearing sequential sentences (condition iii)) with asymmetrical distribution among patients. These results are discussed, principally the correlation between speech discrimination scores and the rCBF distribution in the frontal and temporal lobes.

Evaluation of ocular tumors with technetium-99m-MIBI: planar pinhole technique or SPECT?

OBJECTIVE: This study compares 2 imaging protocols, planar pinhole technique (PPHT) and SPECT, for evaluating ocular masses with 99mTc-MIBI. METHODS: Sixteen patients with ocular lesions were studied. Planar images were acquired 10 min after the injection of 740 MBq 99mTc-MIBI with an LFOV camera fitted with a pinhole collimator (5.0 mm). A SPECT study was performed immediately after the planar study, using a 360 degrees orbit, 64 steps, 20 s/stop, a 128 x 128 matrix, and a low-energy high-resolution (LEHR) collimator. Twelve lesions (9.5-18.0 mm) proved to be malignant: 8 primary tumors (ocular melanoma); 3 local relapses of different tumors of the conjunctiva; and 1 ocular metastasis from breast cancer. The remaining 4 lesions (10.0-16.0 mm) were benign: 1 inflammatory lesion; 1 benign intraocular calcification; and 2 naevi. RESULTS: SPECT images showed 11 of 12 malignant lesions (91.6%), whereas the planar technique demonstrated only 4 of the 12 lesions (33.3%). One false-positive result, the inflammatory lesion, was visualized by both techniques. The remaining benign lesions were not detected with either method. CONCLUSION: Technetium-99m-MIBI SPECT is a sensitive technique for detecting malignant ocular tumors. SPECT imaging is a better alternative to planar imaging for ocular tumors.

Tc-99m isonitrile uptake in a brain metastatic lesion. Comparison with Tc-99m DTPA using planar and SPECT imaging.

Tc-99m isonitrile uptake in a metastatic brain tumor is demonstrated using planar and SPECT imaging. Comparison with Tc-99m DTPA shows a different distribution pattern and uptake intensity, suggesting a different mechanism for both tracers. It is possible that Tc-99m CPI could reflect metabolic activity of the tumor cells and might be useful to evaluate the grade of malignancy as well as the recurrence of brain tumors.