Two-Year Event-Free Survival Prediction in DLBCL Patients Based on In Vivo Radiomics and Clinical Parameters.

Purpose: For the identification of high-risk patients in diffuse large B-cell lymphoma (DLBCL), we investigated the prognostic significance of in vivo radiomics derived from baseline [18F]FDG PET/CT and clinical parameters. Methods: Pre-treatment [18F]FDG PET/CT scans of 85 patients diagnosed with DLBCL were assessed. The scans were carried out in two clinical centers. Two-year event-free survival (EFS) was defined. After delineation of lymphoma lesions, conventional PET parameters and in vivo radiomics were extracted. For 2-year EFS prognosis assessment, the Center 1 dataset was utilized as the training set and underwent automated machine learning analysis. The dataset of Center 2 was utilized as an independent test set to validate the established predictive model built by the dataset of Center 1. Results: The automated machine learning analysis of the Center 1 dataset revealed that the most important features for building 2-year EFS are as follows: max diameter, neighbor gray tone difference matrix (NGTDM) busyness, total lesion glycolysis, total metabolic tumor volume, and NGTDM coarseness. The predictive model built on the Center 1 dataset yielded 79% sensitivity, 83% specificity, 69% positive predictive value, 89% negative predictive value, and 0.85 AUC by evaluating the Center 2 dataset. Conclusion: Based on our dual-center retrospective analysis, predicting 2-year EFS built on imaging features is feasible by utilizing high-performance automated machine learning.

In situ lymphoma imaging in a spontaneous mouse model using the Cerenkov Luminescence of F-18 and Ga-67 isotopes.

Cerenkov luminescence imaging (CLI) is a promising approach to image-guided surgery and pathological sampling. It could offer additional advantages when combined to whole-body isotope tomographies. We aimed to obtain evidence of its applicability in lymphoma patho-diagnostics, thus we decided to investigate the radiodiagnostic potential of combined PET or SPECT/CLI in an experimental, novel spontaneous high-grade B-cell lymphoma mouse model (Bc.DLFL1). We monitored the lymphoma dissemination at early stage, and at clinically relevant stages such as advanced stage and terminal stage with in vivo 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) and 67Ga-citrate single photon emission computed tomography (SPECT)/MRI. In vivo imaging was combined with ex vivo high resolution CLI. The use of CLI with 18F-Fluorine (F-18) and 67Ga-Gallium isotopes in the selection of infiltrated lymph nodes for tumor staging and pathology was thus tested. At advanced stage, FDG PET/MRI plus ex vivo CLI allowed accurate detection of FDG accumulation in lymphoma-infiltrated tissues. At terminal stage we detected tumorous lymph nodes with SPECT/MRI and we could report in vivo detection of the Cerenkov light emission of 67Ga. CLI with 67Ga-citrate revealed lymphoma accumulation in distant lymph node locations, unnoticeable with only MRI. Flow cytometry and immunohistochemistry confirmed these imaging results. Our study promotes the combined use of PET and CLI in preclinical studies and clinical practice. Heterogeneous FDG distribution in lymph nodes, detected at sampling surgery, has implications for tissue pathology processing and it could direct therapy. The results with 67Ga also point to the opportunities to further apply suitable SPECT radiopharmaceuticals for CLI.

Intraperitoneal Glucose Transport to Micrometastasis: A Multimodal In Vivo Imaging Investigation in a Mouse Lymphoma Model.

Bc-DLFL.1 is a novel spontaneous, high-grade transplantable mouse B-cell lymphoma model for selective serosal propagation. These cells attach to the omentum and mesentery and show dissemination in mesenteric lymph nodes. We aimed to investigate its early stage spread at one day post-intraperitoneal inoculation of lymphoma cells (n = 18 mice), and its advanced stage at seven days post-inoculation with in vivo [18F]FDG-PET and [18F]PET/MRI, and ex vivo by autoradiography and Cherenkov luminescence imaging (CLI). Of the early stage group, nine animals received intraperitoneal injections, and nine received intravenous [18F]FDG injections. The advanced stage group (n = 3) received intravenous FDG injections. In the early stage, using autoradiography we observed a marked accumulation in the mesentery after intraperitoneal FDG injection. Using other imaging methods and autoradiography, following the intravenous injection of FDG no accumulations were detected. At the advanced stage, tracer accumulation was clearly detected in mesenteric lymph nodes and in the peritoneum after intravenous administration using PET. We confirmed the results with immunohistochemistry. Our results in this model highlight the importance of local FDG administration during diagnostic imaging to precisely assess early peritoneal manifestations of other malignancies (colon, stomach, ovary). These findings also support the importance of applying topical therapies, in addition to systemic treatments in peritoneal cancer spread.

[The applicability of 123I-FP-CIT SPECT dopamine transporter imaging in clinical practice]. / A 123I-FP-CIT SPECT dopamin transzporter képalkotás jelentosége a klinikai gyakorlatban.

The 123I-FP-CIT dopamine transporter SPECT imaging is a sensitive method to assess functional dopaminergic neuron terminals in the striatum. The method has also been available in Hungary for years. There are two main indications: (i) to help differentiate essential tremor from clinically uncertain Parkinsonism, including patients with early symptoms and (ii) to help differentiate dementia with Lewy bodies from Alzheimer's disease. The aim of this paper is to review 123I-FP-CIT SPECT imaging based on international data/guidelines and our own experiences, thereby assisting nuclear medicine practitioners and neurologists.

The impact of post-radioiodine therapy SPECT/CT on early risk stratification in differentiated thyroid cancer; a bi-institutional study.

OBJECTIVE: SPECT/CT has numerous advantages over planar and traditional SPECT images. The aim of this study was to evaluate the role of post-radioiodine therapy SPECT/CT of patients with differentiated thyroid cancer (DTC) in early risk classification and in prediction of late prognosis. PATIENTS AND METHODS: 323 consecutive patients were investigated after their first radioiodine treatment (1100-3700 MBq). Both whole body scan and SPECT/CT images of the head, neck, chest and abdomen regions were taken 4-6 days after radioiodine therapy. Patients were re-evaluated 9-12 months later as well as at the end of follow up (median 37 months). RESULTS: Post-radioiodine therapy SPECT/CT showed metastases in 22% of patients. Lymph node, lung and bone metastases were detected in 61, 13 and 5 patients, respectively, resulting in early reclassification of 115 cases (36%). No evidence of disease was found in 251 cases at 9-12 months after radioiodine treatment and 269 patients at the end of follow-up. To predict residual disease at the end of follow-up, the sensitivities, specificities and diagnostic accuracies of the current risk classification systems and SPECT/CT were: ATA: 77%, 47% and 53%; ETA: 70%, 62% and 64%; SPECT/CT: 61%, 88% and 83%, respectively. There was no difference between cohorts of the two institutions when data were analyzed separately. CONCLUSIONS: Based on our bi-institutional experience, the accuracy of post-radioiodine SPECT/CT outweighs that of the currently used ATA and ETA risk classification systems in the prediction of long-term outcome of DTC.

Validation of an automated morphological MRI-based (123)I-FP-CIT SPECT evaluation method.

INTRODUCTION: Dopamine transporter imaging with (123)I-FP-CIT single photon emission computed tomography (SPECT) is helpful for the differential diagnosis between Parkinsonian syndrome (PS) and essential tremor (ET). Although visual assessment and time-consuming manual evaluation techniques are readily available, a fully objective and automated dopamine transporter quantification technique is always preferable, at least in research and follow-up investigations. Our aim was to develop a novel automated magnetic resonance imaging (MRI)-based evaluation technique of dopamine transporter SPECT images and to compare its diagnostic accuracy with those of the gold-standard visual grading and manual dopamine transporter binding quantification methods. METHODS: (123)I-FP-CIT SPECT and MRI sessions were conducted in 33 patients with PS (15 men; mean age: 60.3 ± 9.7 years) and 15 patients with ET (8 men; mean age: 54.7 ± 16.3 years). Striatal dopamine transporter binding was visually classified by 2 independent experts as normal or abnormal grade I, II and III. Caudal and putaminal specific uptake ratios were calculated by both automated MRI-based and manual evaluation techniques. RESULTS: We found almost perfect agreement (κ = 0.829) between the visual scores by the 2 observers. The automated method showed strong correlation with the visual and manual evaluation techniques and its diagnostic accuracy (sensitivity = 97.0%; specificity = 93.3%) was also comparable to these methods. The automatically determined uptake parameters showed negative correlation with the clinical severity of parkinsonism. Based on ordinal regression modelling, the automated MRI-based method could reliably determine the visual grading scores. CONCLUSION: The novel MRI-based evaluation of (123)I-FP-CIT SPECT images is useful for the differentiation of PS from ET.

[New trends and novel possibilities in the clinical use of SPECT/CT imaging]. / Újdonságok és új lehetoségek a SPECT/CT klinikai alkalmazásában.

The application of hybrid equipments and fused techniques has increasing importance in the field of imaging diagnostics. The biggest advantage of these methods is the simultaneous use of several modalities which can give data about the morphological, functional as well as molecular changes of the different diseases at the same time. The facilities, advantages and the applicability of the SPECT/CT (single photon emission computer tomograph/computer tomograph) are summarized in this paper mainly in oncologic diseases, but also in other disorders. The multimodality equipments showing the function and morphology together increase the specificity and diagnostic accuracy of the nuclear medicine methods and were found to be more efficient in the therapy effectiveness, too.

[SPECT radiopharmaceuticals -- novelties and new possibilities]. / SPECT-radiofarmakonok -- újdonságok és új lehetoségek.

Actual state of affairs and future perspectives of SPECT radiopharmaceuticals regarding local and international data were summarized. Beyond conventional gamma-emitting radioisotopes, localization studies with beta emitting therapeutic radiopharmaceuticals hold increasing importance. Extension of hybrid (SPECT/CT) equipments has modified conventional scintigraphic and SPECT methods as well but more important changes come into the world through novel ligands for specific diagnoses and therapy.

"Platelet-associated regulatory system (PARS)" with particular reference to female reproduction.

BACKGROUND: Blood platelets play an essential role in hemostasis, thrombosis and coagulation of blood. Beyond these classic functions their involvement in inflammatory, neoplastic and immune processes was also investigated. It is well known, that platelets have an armament of soluble molecules, factors, mediators, chemokines, cytokines and neurotransmitters in their granules, and have multiple adhesion molecules and receptors on their surface. METHODS: Selected relevant literature and own views and experiences as clinical observations have been used. RESULTS: Considering that platelets are indispensable in numerous homeostatic endocrine functions, it is reasonable to suppose that a platelet-associated regulatory system (PARS) may exist; internal or external triggers and/or stimuli may complement and connect regulatory pathways aimed towards target tissues and/or cells. The signal (PAF, or other tissue/cell specific factors) comes from the stimulated (by the e.g., hypophyseal hormones, bacteria, external factors, etc.) organs or cells, and activates platelets. Platelet activation means their aggregation, sludge formation, furthermore the release of the for-mentioned biologically very powerful factors, which can locally amplify and deepen the tissue specific cell reactions. If this process is impaired or inhibited for any reason, the specifically stimulated organ shows hypofunction. When PARS is upregulated, organ hyperfunction may occur that culminate in severe diseases. CONCLUSION: Based on clinical and experimental evidences we propose that platelets modulate the function of hypothalamo-hypophyseal-ovarian system. Specifically, hypothalamic GnRH releases FSH from the anterior pituitary, which induces and stimulates follicular and oocyte maturation and steroid hormone secretion in the ovary. At the same time follicular cells enhance PAF production. Through these pathways activated platelets are accumulated in the follicular vessels surrounding the follicle and due to its released soluble molecules (factors, mediators, chemokines, cytokines, neurotransmitters) locally increase oocyte maturation and hormone secretion. Therefore we suggest that platelets are not only a small participant but may be the conductor or active mediator of this complex regulatory system which has several unrevealed mechanisms. In other words platelets are corpuscular messengers, or are more than a member of the family providing hemostasis.

Neuroimaging and cognitive changes during déjà vu.

OBJECTIVE: The cause or the physiological role of déjà vu (DV) in healthy people is unknown. The pathophysiology of DV-type epileptic aura is also unresolved. Here we describe a 22-year-old woman treated with deep brain stimulation (DBS) of the left internal globus pallidus for hemidystonia. At certain stimulation settings, DBS elicited reproducible episodes of DV. METHODS: Neuropsychological tests and single-photon-emission computed tomography (SPECT) were performed during DBS-evoked DV and during normal DBS stimulation without DV. RESULTS: SPECT during DBS-evoked DV revealed hyperperfusion of the right (contralateral to the electrode) hippocampus and other limbic structures. Neuropsychological examinations performed during several evoked DV episodes revealed disturbances in nonverbal memory. CONCLUSION: Our results confirm the role of mesiotemporal structures in the pathogenesis of DV. We hypothesize that individual neuroanatomy and disturbances in gamma oscillations or in the dopaminergic system played a role in DBS-elicited DV in our patient.

Varying appearance of focal nodular hyperplasia in nuclear medicine imaging.

The focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor, which contains variable quantities of normal hepatic cellular elements: Kupffer cells, hepatocytes, bile ducts, and blood vessels. Two patients with suspicion of FNH were investigated by colloidal, blood pool, and hepatobiliary scintigraphy. Dynamic perfusion examination (with labeled RBCs), planar and SPECT studies were performed in all cases. Diagnosis was confirmed by histologic examination. We suggest the importance of combined imaging because of various appearance of the tumor. In our experience SPECT imaging after a planar study is a useful sequence, especially in small tumors in the exact location of activity.

Sentinel lymph nodes in gynaecological malignancies: frontline between TNM and clinical staging systems?

Numerous investigations have recently proved the importance of sentinel lymph node detection in various malignant tumours. It is widely accepted that this procedure is to be recommended only in patients with early stage tumours. The lymph node status and prognosis are closely related. Appropriate staging is essential in the management of malignant tumours and should be individualised. In many cases, the nodal status does not correlate with the clinical stage of the disease. In this survey, we consider some of the most common gynaecological malignancies and the type of staging most appropriate to them. Differences between these staging systems, and controversies concerning them, are related to the concept of sentinel lymph node investigation. The authors believe that sentinel node sampling is in fact a beneficial method in both early and advanced stage disease for determination of the tumour status and individualisation of surgical interventions.

[Diagnostic value of 99mTc-methoxy-isobutyl-isonitril and 99mTc-methylene diphosphonate scintimammography in the preoperative evaluation of breast cancer]. / A 99mTc-metoxi-izobutil-izonitril- és 99mTc-metilén-difoszfonát-szcintimammográfiák diagnosztikus értéke az emlótumorok preoperatív vizsgálatában.

AIM: To compare and establish the value of 99mTc-MIBI (methoxyisobutiylisonitrile) and 99mTc-MDP (methylene diphosphonate) scintigraphy in patients with suspicion of breast cancer. PATIENTS AND METHODS: The study included 105 patients. All patients were evaluated before surgery by 99mTc-MIBI and 99mTc-MDP scintigraphy. Thoracic SPECT study (Multispect II, Siemens) was performed 10 min. after i.v. injection of 99mTc-MIBI and 2 hours after i.v. injection of 99mTc-MDP. Final diagnosis was achieved after operation by histology. RESULTS: 99mTc-MIBI scintigraphy showed a better sensitivity (87%) than the 99mTc-MDP scintigraphy (81%) and the results are similar in specificity and validity, too. CONCLUSIONS: The results suggest that 99mTc-MIBI scintigraphy is a useful method in the preoperative diagnosis of patients with suspicion of breast cancer.

Preliminary experiences with sentinel lymph node detection in cases of vulvar malignancy.

Lymph node status is the most important prognostic factor in vulvar malignancy. The aim of this pilot study was to explore the clinical significance of radionuclide lymphoscintigraphy in the management of vulvar neoplasms. Eight patients with squamous cell carcinoma and two patients with malignant melanoma of the vulva were studied with 100 MBq technetium-99m nanocolloid (Sentiscint, OSSKI, Budapest) 1 day before surgery. The location of the sentinel lymph node was checked by a single-head gamma camera-computer system (MB 9200, Mediso, Budapest). Vulvectomy with bilateral inguinofemoral lymphadenectomy was performed in each case. At lymphadenectomy, the sentinel lymph node was separately removed and histologically studied. Three of the ten patients had positive sentinel lymph nodes (micrometastasis). Five months later one of them had local recurrence of the vulvar cancer, and another had inguinal recurrence of the tumour 6 months postoperatively; the third patient was operated on only recently. Our preliminary results are impressive and suggest that lymphoscintigraphy is an easy and reliable method for detection of the sentinel lymph node in vulvar malignancy.