The ß- radio-guided surgery: Method to estimate the minimum injectable activity from ex-vivo test.

PURPOSE: Radio-guided surgery with ß- decays is a novel technique under investigation. One of the main advantages is its capability to detect small (⩽0.1 ml) samples after injecting the patient with low activity of radiopharmaceutical. This paper presents an experimental method to quantify this feature based on ex-vivo tests on specimens from meningioma patients. METHODS: Patients were enrolled on the basis of the standard uptake value (SUV) and the tumour-to-non-tumour activity ratio (TNR) resulted from 68Ga-DOTATOC PET exams. After injecting the patients with 93-167 MBq of 90Y-DOTATOC, 26 samples excised during surgery were analyzed with a ß- probe. The radioactivity expected on the neoplastic specimens was estimated according to the SUV found in the PET scan and the correlation with the measured counts was studied. The doses to surgeon and medical personnel were also evaluated. RESULTS: Even injecting as low as 1.4 MBq/kg of radiotracer, tumour residuals of 0.1 ml can be detected. A negligible dose to the medical personnel was confirmed. CONCLUSIONS: Radio-guided surgery with ß- decays is a feasible technique with a low radiation dose for both personnel and patient, in particular if the patient is injected with the minimum required activity. A correlation greater than 80% was observed between the measured counts and the expected activity for the lesion samples based on the individual SUV and the TNR. This makes identifiable the minimum injectable radiotracer activity for cases where 90Y is the utilized radionuclide.

First ex vivo validation of a radioguided surgery technique with ß-radiation.

PURPOSE: A radio-guided surgery technique with ß(-)-emitting radio-tracers was suggested to overcome the effect of the large penetration of γ radiation. The feasibility studies in the case of brain tumors and abdominal neuro-endocrine tumors were based on simulations starting from PET images with several underlying assumptions. This paper reports, as proof-of-principle of this technique, an ex vivo test on a meningioma patient. This test allowed to validate the whole chain, from the evaluation of the SUV of the tumor, to the assumptions on the bio-distribution and the signal detection. METHODS: A patient affected by meningioma was administered 300MBq of (90)Y-DOTATOC. Several samples extracted from the meningioma and the nearby Dura Mater were analyzed with a ß(-) probe designed specifically for this radio-guided surgery technique. The observed signals were compared both with the evaluation from the histology and with the Monte Carlo simulation. RESULTS: we obtained a large signal on the bulk tumor (105cps) and a significant signal on residuals of ∼0.2ml (28cps). We also show that simulations predict correctly the observed yields and this allows us to estimate that the healthy tissues would return negligible signals (≈1cps). This test also demonstrated that the exposure of the medical staff is negligible and that among the biological wastes only urine has a significant activity. CONCLUSIONS: This proof-of-principle test on a patient assessed that the technique is feasible with negligible background to medical personnel and confirmed that the expectations obtained with Monte Carlo simulations starting from diagnostic PET images are correct.

Use of the FLUKA Monte Carlo code for 3D patient-specific dosimetry on PET-CT and SPECT-CT images.

Patient-specific absorbed dose calculation for nuclear medicine therapy is a topic of increasing interest. 3D dosimetry at the voxel level is one of the major improvements for the development of more accurate calculation techniques, as compared to the standard dosimetry at the organ level. This study aims to use the FLUKA Monte Carlo code to perform patient-specific 3D dosimetry through direct Monte Carlo simulation on PET-CT and SPECT-CT images. To this aim, dedicated routines were developed in the FLUKA environment. Two sets of simulations were performed on model and phantom images. Firstly, the correct handling of PET and SPECT images was tested under the assumption of homogeneous water medium by comparing FLUKA results with those obtained with the voxel kernel convolution method and with other Monte Carlo-based tools developed to the same purpose (the EGS-based 3D-RD software and the MCNP5-based MCID). Afterwards, the correct integration of the PET/SPECT and CT information was tested, performing direct simulations on PET/CT images for both homogeneous (water) and non-homogeneous (water with air, lung and bone inserts) phantoms. Comparison was performed with the other Monte Carlo tools performing direct simulation as well. The absorbed dose maps were compared at the voxel level. In the case of homogeneous water, by simulating 10(8) primary particles a 2% average difference with respect to the kernel convolution method was achieved; such difference was lower than the statistical uncertainty affecting the FLUKA results. The agreement with the other tools was within 3­4%, partially ascribable to the differences among the simulation algorithms. Including the CT-based density map, the average difference was always within 4% irrespective of the medium (water, air, bone), except for a maximum 6% value when comparing FLUKA and 3D-RD in air. The results confirmed that the routines were properly developed, opening the way for the use of FLUKA for patient-specific, image-based dosimetry in nuclear medicine.

Kidney dosimetry in ¹77Lu and 9°Y peptide receptor radionuclide therapy: influence of image timing, time-activity integration method, and risk factors.

Kidney dosimetry in (177)Lu and (90)Y PRRT requires 3 to 6 whole-body/SPECT scans to extrapolate the peptide kinetics, and it is considered time and resource consuming. We investigated the most adequate timing for imaging and time-activity interpolating curve, as well as the performance of a simplified dosimetry, by means of just 1-2 scans. Finally the influence of risk factors and of the peptide (DOTATOC versus DOTATATE) is considered. 28 patients treated at first cycle with (177)Lu DOTATATE and 30 with (177)Lu DOTATOC underwent SPECT scans at 2 and 6 hours, 1, 2, and 3 days after the radiopharmaceutical injection. Dose was calculated with our simplified method, as well as the ones most used in the clinic, that is, trapezoids, monoexponential, and biexponential functions. The same was done skipping the 6 h and the 3 d points. We found that data should be collected until 100 h for (177)Lu therapy and 70 h for (90)Y therapy, otherwise the dose calculation is strongly influenced by the curve interpolating the data and should be carefully chosen. Risk factors (hypertension, diabetes) cause a rather statistically significant 20% increase in dose (t-test, P < 0.10), with DOTATATE affecting an increase of 25% compared to DOTATOC (t-test, P < 0.05).

Calculation of electron and isotopes dose point kernels with FLUKA Monte Carlo code for dosimetry in nuclear medicine therapy.

PURPOSE: The calculation of patient-specific dose distribution can be achieved by Monte Carlo simulations or by analytical methods. In this study, FLUKA Monte Carlo code has been considered for use in nuclear medicine dosimetry. Up to now, FLUKA has mainly been dedicated to other fields, namely high energy physics, radiation protection, and hadrontherapy. When first employing a Monte Carlo code for nuclear medicine dosimetry, its results concerning electron transport at energies typical of nuclear medicine applications need to be verified. This is commonly achieved by means of calculation of a representative parameter and comparison with reference data. Dose point kernel (DPK), quantifying the energy deposition all around a point isotropic source, is often the one. METHODS: FLUKA DPKS have been calculated in both water and compact bone for monoenergetic electrons (10-3 MeV) and for beta emitting isotopes commonly used for therapy (89Sr, 90Y, 131I 153Sm, 177Lu, 186Re, and 188Re). Point isotropic sources have been simulated at the center of a water (bone) sphere, and deposed energy has been tallied in concentric shells. FLUKA outcomes have been compared to PENELOPE v.2008 results, calculated in this study as well. Moreover, in case of monoenergetic electrons in water, comparison with the data from the literature (ETRAN, GEANT4, MCNPX) has been done. Maximum percentage differences within 0.8.RCSDA and 0.9.RCSDA for monoenergetic electrons (RCSDA being the continuous slowing down approximation range) and within 0.8.X90 and 0.9.X90 for isotopes (X90 being the radius of the sphere in which 90% of the emitted energy is absorbed) have been computed, together with the average percentage difference within 0.9.RCSDA and 0.9.X90 for electrons and isotopes, respectively. RESULTS: Concerning monoenergetic electrons, within 0.8.RCSDA (where 90%-97% of the particle energy is deposed), FLUKA and PENELOPE agree mostly within 7%, except for 10 and 20 keV electrons (12% in water, 8.3% in bone). The discrepancies between FLUKA and the other codes are of the same order of magnitude than those observed when comparing the other codes among them, which can be referred to the different simulation algorithms. When considering the beta spectra, discrepancies notably reduce: within 0.9.X90, FLUKA and PENELOPE differ for less than 1% in water and less than 2% in bone with any of the isotopes here considered. Complete data of FLUKA DPKS are given as Supplementary Material as a tool to perform dosimetry by analytical point kernel convolution. CONCLUSIONS: FLUKA provides reliable results when transporting electrons in the low energy range, proving to be an adequate tool for nuclear medicine dosimetry.

Dosimetry for treatment with radiolabelled somatostatin analogues. A review.

Peptide Receptor Radionuclide Therapy (PRRT) has proven its efficacy in the treatment of neuroendocrine and other somatostatin receptor expressing tumours (SR-tumours). Several clinical trials have confirmed that adverse effects are represented by possible renal impairment, which is the major concern, and low but not absent hematological toxicity. High kidney irradiation is a constant, despite the sparing of dose obtained by renal protectors. Hematological toxicity, although low, needs to be monitored. The clinical and dosimetry results collected in more than a decade have recognized weak points to unravel, increased knowledge, offering new views. When planning therapy with radiopeptides, the large patients' variability as for biodistribution and tumour uptake must be taken into account in order to tailor the therapy, or at least to avoid foreseeable gross treatments. Reliable and personalized dosimetry is more and more requested. This paper reviews through the literature the methods to study the biokinetics, the dosimetry outcomes, some clue information and correlations obtained once applying the radiobiological models. Special focus is given on recent improvements and indications for critical organ protection that light up challenging perspectives for PRRT.

Eyelid sebaceous gland carcinoma in a young Caucasian man.

BACKGROUND: Eyelid sebaceous gland carcinoma is rarely observed in young Caucasian men. HISTORY AND SIGNS: A 28-year-old man was referred for a recurring chalazion of the eyelid that had been operated four times in the past two years. The chalazion-like lesion of the external third of the upper left eyelid was associated with a cystic lesion. Cytology of the fluid in the cyst and histology of the lesion were compatible with a sebaceous cell carcinoma. Magnetic resonance imaging revealed that the cystic lesion associated with the eyelid tumour was extending into the orbit. THERAPY AND OUTCOME: According to current clinical practice and experience, to increase the chance of survival of the patient, an orbital exenteration was conducted to remove the sebaceous cell carcinoma in total. CONCLUSIONS: Although rare, one should be aware that an eyelid sebaceous cell carcinoma can occur in a young Caucasian man and this diagnosis should be evoked in case of a recurrent chalazion.

[Orbital metastasis in malignant melanoma]. / Métastases orbitaires de mélanome malin.

We report the case of a 60-year-old man presenting bilateral progressive proptosis with diplopia, weight loss, tachycardia, nervosity, and stomach pain. These signs seemed at first to favor a diagnosis of Graves'ophthalmopathy. Thyroid tests were negative and the initial orbital CT scan was considered normal. A new radiological investigation 4 months later in our hospital revealed typical hypertrophy of the extraocular muscles compatible with orbital metastasis. The systemic investigations demonstrated a pulmonary tumor, multiple hepatic lesions, and several pigmented nodules of gastric mucosa. The pathology of pulmonary and gastric specimens confirmed the diagnosis of malignant melanoma. The primary lesion remains unknown. The authors discuss the differential diagnoses of orbital metastasis and the radiological characteristics of orbital metastasis in malignant melanoma.

[Varicella zoster virus and atypical necrotizing retinopathies in HIV and AIDS patients]. / Varicella-Zoster-Virus und atypische nekrotisierende Retinopathien bei HIV- und AIDS-Patienten.

BACKGROUND: Necrotizing retinopathies of suspected viral origin, but which do not meet the criteria for either CMV-retinitis or acute retinal necrosis syndrome, have been grouped together under the term atypical necrotizing retinopathies. Nothing is known about their etiology. PATIENTS AND METHODS: Aqueous humor samples were drawn from two HIV-positive and eight patients with AIDS presenting with an atypical necrotizing retinopathy, additionally from six patients with acute retinal necrosis syndrome and 28 patients with active CMV-retinitis at the time of diagnosis as well as from thirty healthy controls at surgery. All samples underwent DNA extraction and amplification for viral DNA of HSV-1, VZV and CMV. RESULTS: VZV-DNA was detected in seven of nine aqueous humor samples derived from patients with atypical necrotizing retinopathies and in four of six samples from patients with acute retinal necrosis syndrome, but not in any one from the 28 patients with CMV retinitis. In the latter group, CMV DNA was detectable in 23 samples, in two of these additionally HSV-1 DNA. No viral DNA was amplified from any of the samples from healthy controls. CONCLUSIONS: Varicella zoster virus ist the leading cause of atypical necrotizing retinopathies. This should be considered in the antiviral chemotherapy. Moreover, we were able to establish the diagnosis using DNA amplification for the viruses of the herpes family irrespective of the etiology in 80% of necrotizing retinopathies.

Acute metabolic alkalosis in cystic fibrosis: prospective study and review of the literature.

Between January 1993 and April 1994, 5 patients with cystic fibrosis, aged 4-9 months, were admitted to the Department of Pediatrics, University of Berne, Switzerland, with acute, severe metabolic alkalosis (sodium < 133 mmol/l, plasma potassium < 3.5, chloride < 85, bicarbonate > 35.0 mmol/l, blood pH > 7.43). 87 cases of acute metabolic alkalosis complicating cystic fibrosis reported in the literature between 1951 and 1995 were also reviewed. Our cases and those described in the literature demonstrate that acute metabolic alkalosis occurs in patients aged 2 years or less. Anorexia, vomiting, respiratory exacerbation, fever, and body weight loss often precede metabolic alkalosis. Furthermore, metabolic alkalosis is a common initial presentation of cystic fibrosis, suggesting that this diagnosis should be considered in the context of unexplained metabolic alkalosis.

[The evaluation of the physical characteristics of a volumetric computer tomograph]. / Valutazione delle caratteristiche fisiche di un tomografo computerizzato volumetrico.

Spiral or volumetric computed tomography (CT) is a new scanning technique which allows the scanning of body regions with a continuously rotating system based on the slip ring technology; the patient is also moved continuously, synchronously with data acquisition. The physical characteristics of spiral CT image acquisition were compared with those of conventional CT images. The modulation transfer function (MTF) has the same values for medium-resolution filters, but lower values for spiral CT for high-resolution and frequency-enhancement filters. The slice sensitivity profile (SSP) describes the longitudinal image resolution for multiplanar reconstructions and was measured in terms of FWHM of the SSP curve. We obtained, for 10-mm slice thickness, a FWHM = 10.4 mm (conventional CT), versus 10.7 mm (Spiral CT), while, for 5-mm slice thickness, the corresponding values were 5.2 mm (conventional CT) and 5.5 mm (spiral CT). Noise was evaluated simply by measuring the standard deviation of the CT numbers, in a region of interest, of a uniform image and with the power spectrum or Wiener spectrum of the same image. To assess overall image quality and yield, the noise equivalent quanta (NEQ) value was also calculated. The values were a little lower for the spiral technique, particularly with high-resolution and enhancement or convolution filters. Dosimetric evaluation of the computed tomography dose index (CTDI) and of the multiple scan average dose (MSAD) was done using an acquisition protocol for average lung dose, in an anthropomorphic phantom and with TL dosimeters. The MSAD was 6.17 +/- 0.20 cGy for conventional CT and 5.98 +/- 0.23 cGy for Spiral CT, while lung dose was 3.25 +/- 0.12 cGy and 3.01 +/- 0.16 cGy, respectively.

Chronic metabolic alkalosis: not uncommon in young children with severe cystic fibrosis.

The acid-base balance of 199 patients with cystic fibrosis, seen from 1987 through 1992 at the Bern Outpatient Clinic, were evaluated. Simple metabolic alkalosis was demonstrated in 16 and mixed metabolic alkalosis and respiratory acidosis in 9 patients. When compared with 10 patients with simple respiratory acidosis and 16 with normal hydrogen ion balance, those with simple metabolic alkalosis were significantly younger. The need for pancreatic enzymes was significantly higher and the relative underweight significantly more severe in patients with either simple or mixed metabolic alkalosis and respiratory acidosis. The results indicate the rather common occurrence of chronic metabolic alkalosis in cystic fibrosis. It is observed in young patients, in patients who need high doses of pancreatic enzymes and in the those with poor nutritional status.

[Digital storage phosphor radiography. Doses and image quality]. / Radiografia digitale con fosfori. Dose e qualità delle immagini.

Digital radiography (DR) based on storage phosphor technology is progressively replacing conventional screen-film system radiographic techniques (CR). However, many questions about image quality and dose reduction are still open. Thus, since DR spatial resolution is always lower than that of high quality screen-film images and image noise is conversely higher, for general radiography examinations especially, the signal-to-noise ratio is always lower with DR than with CR at the same dose level. However, the wide dynamic range, the linear response of storage phosphor detectors and the automatic read-out control of the digital system, enable lower DR X-ray imaging efficiency to be overcome, producing a nearly perfect readout of the image data every time an exposure is made. Moreover, post-processing can make the detection of abnormalities easier. This is why in many ROC clinical accuracy studies DR performed equally or better than CR. Good quality DR images, similar to conventional ones at the same dose levels, are therefore achievable in chest, abdomen, bone and soft-tissues examinations. Dose evaluation protocols are strongly needed in DR since overexposures due to technical mistakes may be overlooked; moreover, doses can be adjusted to the peculiar diagnostic need. The S values shown on any hard-copy image can be used to this purpose, even though it must be pointed out that they do not express the actual mean dose to the detector.

The choice of radiographic film-screen systems: quality evaluation and purchasing specifications drafting. Report on A.I.F.B. Working Group activity.

The comparative evaluation of radiographic screen-film systems presents several problems from both the theoretical and the experimental points of view. From the theoretical point of view the main difficulties are related to the choice of the parameters best suited to express the "overall quality" of a system. This quantity is expressed as a product of image quality index and system sensitivity. As image quality index we assumed the signal-to-noise power ratio: this index depends in an explicit way on contrast, resolution and noise of the system. From the experimental point of view the main problem is that to measure some basic quantities, sophisticated and expensive equipment, like computer-controlled microdensitometers, is generally required. In this paper, we report the Italian Association of Biomedical Physicists Task group suggestions for measuring the basic physical parameters (with particular reference to the use of cost-effective equipment and for purchasing specification drafting). Using synthetic quality indices, the evaluation criteria of radiographic materials are directly derived from the general theory of radiographic image perception.

[Digital radiography with phosphorus memory: verification of the centering of the patient in high-energy radiotherapy]. / Radiografia digitale con fosfori a memoria: verifica della centratura del paziente nella radioterapia con alte energie.

A digital radiographic system using storage phosphor detectors was employed in order to verify radiotherapy treatments with high energy photon beams (60Co-18 MV X-rays). The wide range linearity of the detectors and also the possibility of digital image post-processing allowed portal films to be obtained with sufficient contrast in all treatment techniques, particularly in the case of mantle fields. The use of digital radiography may become an easy and valuable procedure for therapy verification.

[Digital radiography in urography]. / La radiografia digitale in urografia.

The clinical utility was evaluated of a computed radiographic system in urography. The system (FCR 101, Philips Medical Systems, Inc., Shelton, CT) is based on a photo-stimulatable phosphor screen (imaging plate) for X-ray image detection and storage. The X-ray information recorded on the imaging plate is converted into digital from and processed by means of a computer. After processing is completed, the digitized image is reversed back to analogic signals, which modulate the intensity of a laser beam scanning the image on a single-emulsion film (Fuji CR 633). Two hundred IVP's were obtained in four groups, of 50 patients each, with normal azotemic values by rapid infusion of a low osmolality contrast medium (iopamidol 150 mgI/ml). While conventional radiographs were performed on the first group of patients with the injection of 0.6 gI/kg body weight of contrast medium, digital examinations were carried out, in the remaining three groups, with the injection of 0.6, 0.3 and 0.12 gI/kg, respectively. The digital images were processed with the "Abdomen-routine" program. A specific algorithm was implemented in order to reduce the excessive contrast resolution of the bladder, which is due to the characteristics of the nonionic contrast medium and enhanced by the reading program. The image details were evaluated by two observers and then statistically analyzed with nonparametric tests. Statistical analysis did not show any difference in the quality of digital and screen-film images. Image processing improved some inadequate images, by reducing the contrast resolution of the bladder, and allowed a better detection of some details. Low doses (0.3 gI/kg) of a low osmolality (150 mgI/kg) contrast medium were enough to obtain good images. Another biological advantage was obtained by a consistent radiation dose reduction (about 40%).