High resolution small animal single photon emission computed tomography: uptake of [99mTc]bombesin and [123I]ioflupane by rat brain.

AIM: The aims of this study were: 1) to perform brain single photon emission computed tomography (SPECT) in anesthetized rats with high resolution cameras (HRC) equipped with parallel hole collimation resolution of about 1 mm (HRC1) and 2 mm (HRC2); 2) to assess when and with which radio-tracer HRC1 SPECT shows advantages over HRC2. METHODS: We used two multicrystal HRCs with parallel square hole collimators, whose pure tungsten septa closely fit the crystals, in turn matched with a 4 inch2 position sensitive photomultiplier. HRC1 showed 1.1 mm and HCR2 2.1 mm resolution at collimator contact. HRCs performed 180 degrees semi-circular orbits around the head of rats: image reconstruction occurred with ordered subsets expectation maximization algorithms. Resolution of SPECT was measured with a Derenzo Phantom, resulting 1.4 mm for HRC1 and 2.3 mm for HRC2. Three rats were studied with [(99m)Tc]HMPAO, 3 rats with [(99m)Tc]bombesin (BN) and 48 h later with [(123)I]ioflupane (DaTSCAN). SPECT studies were reviewed by two experienced operators. RESULTS: Technetium-99m-HMPAO SPECT showed similar images with HRC1 and HRC2. The uptake of BN by amygdale, hippocampus and olfactory tract was detected by both cameras. DaTSCAN SPECT with HRC1 showed detailed image of the tail of the caudatus: this image was not obtained with HRC2. DaTSCAN and BN SPECT showed amygdale with both HRCs. However, only the central nucleus of amygdale takes up DaTSCAN, whereas central, lateral and basolateral amygdaloid nuclei express BN receptors. Only HRC1 SPECT showed amygdale larger with BN than with DaTSCAN. CONCLUSION: Spatial resolution of 1.4 mm is appropriate to detect selected subcerebral structures.

High resolution mini-gammacamera and 99mTc [HMPAO] - leukocytes for diagnosis of infection and radioguided surgery in diabetic foot.

Discovery of osteitis may be delayed because of late appearance of X-ray signs in patients with diabetic foot. Scintigraphy with labelled leukocytes is able to detect flogosis but often misses bone involvement, due to inadequate resolution of Anger camera, the commonest detector used in nuclear medicine. Radioguided surgery and biopsy with high resolution scintigraphy (HRS) started to be studied since 2000: although this method had never been tested for planning and guiding diabetic foot surgery, in our opinion it can help early diagnosis and surgical treatment of diabetic foot. Five patients with diabetic foot and suspected infection were studied with standard 99mTc [HMPAO]-leukocyte scan. In the same patients 2 mm spatial resolution HRS was performed 24 hours after administration of labelled WBC, using our inch2 field-of-view portable mini-gammacamera. Operations were done just after the 24h scan and were guided with the portable high resolution device in the four patients who showed positive scan. Scintigraphy with Anger camera and HRS were positive in four patients. HRS showed a bar-shaped radioactivity corresponding to small phalanges, close to the main inter-digital hot spot. The presence of osteitis on phalanges that had been shown by HRS was confirmed at surgery, that was successfully driven with the high resolution mini-camera. In conclusion HRS is able to diagnose early osteitis of diabetic foot and to guide diabetic foot surgery.

99MTC [13LEU] bombesin and a new gamma camera, the imaging probe, are able to guide mammotome breast biopsy.

UNLABELLED: A pilot study has been carried out in order to verify the feasibility of scintigraphic driving for breast biopsy. A new high resolution (HR) gamma ray detector, the imaging probe (IP), and 99mTc [13Leu] Bombesin (99mTc BN), have been used to drive a mammotome biopsy needle after having fused radioisotope with digital X-ray images. IP is a mobile, high resolution, miniaturised gamma camera, whose field of view is one inch and whose spatial resolution is 2 mm. 99mTc BN is a new radiotracer derived from the well-known peptide, that has already shown very high sensitivity in detecting breast cancer. PATIENTS AND METHODS: Five patients very suspicious for breast cancer were studied. 185 MBq of 99mTc BN were i.v. injected and dynamic prone scintimammography was performed for 20 minutes with a conventional large field of view gamma camera. IP was matched with the biopsy system and digital X-ray device of a mammotome system, in order to fuse images and to use the mammotome pointer indifferently on X-ray, scintigraphic and fused images. Biopsy samples were counted and weighed: uptake was expressed as counts sec-1 gr-1. Samples were classified into high, intermediate and low uptake. Conventional histological assessment was blindly performed on the samples. RESULTS: All of the patients showed cancer. The T categorisation was T1a for two cancers and T1b for 3. Dynamic prone scintimammography with conventional gamma camera, as well as HR scintigraphy with IP showed spots of 99mTc BN uptake. Maximal mismatch between X-ray lesions and of hot spots imaged with IP before mammotome scintigraphy was 3.4 mm. All the high uptake samples and all but two of the intermediate uptake samples showed cancer, whereas histology found malignant tissue in only 2 out of the 8 low uptake samples. CONCLUSION: 99mTc BN confirms its high sensitivity in detecting breast cancer. IP is able to drive or co-drive breast biopsy when used with appropriate radiopharmaceuticals.

Clinical use of an imaging probe in breast cancer surgery.

AIMS: Portable cameras allow easy transfer of the detector, and thus of radioisotope imaging, to the operating room. In this paper we describe our preliminary experience in radionuclide imaging of breast cancer with a 22.8 x 22.8 mm(2) field-of-view minicamera called "Imaging Probe" (IP). METHODS: Breast cancer detection by IP was performed to guide biopsy, in particular open biopsy, or help fine-needle or core-needle positioning when the main guidance method was ultrasonography or digital radiography. 99mTc Sestamibi (MIBI) was injected 1 h before imaging and biopsy to 14 patients with suspected or known breast cancer. Scintigraphic images were acquired before and after biopsy in each patient. The surgeon was allowed to take into account scintigraphic images as well as previously performed mammograms and ultrasonography. RESULTS: High-resolution IP images were able to guide biopsy toward cancer or toward washout zones of cancer which are thought to be chemoresistant in seven patients out of 10. Four patients in whom IP and MIBI were unable to guide biopsy were found not to have cancer. CONCLUSIONS: Our study confirms the ability of IP to guide breast biopsy even when our minicamera has to be handled manually by trained physicians during surgery.

New localization technique for breast cancer biopsy: mammotome guidance with imaging probe.

AIMS AND BACKGROUND: The "Imaging Probe" (IP) is a small, portable, high-resolution gamma camera to be used in radioguided surgery. The present work discusses a special prototype designed for guiding biopsies. The IP was mounted to a Fischer digital X-ray stereotactic core biopsy system in such a way that biopsy could be guided simultaneously by X-ray stereotaxis and 99mTc-Sestamibi (MIBI) images from IP. METHODS: The IP field of view was 22.8 x 22.8 mm(2), with a spatial resolution of approx. 2.5 mm. We used off-line software for image fusion on a dedicated Pentium III portable PC. It was matched with a Fischer digital X-ray stereotactic biopsy system dedicated to direct the mammotome towards breast opacities. The operator was allowed to slightly correct the direction of the mammotome needle taking into account stereotactic X-ray, scintigraphic and fused images. Biopsy samples were counted by IP before they were sent to the pathologist. RESULTS: High-resolution IP scintigraphy showed substantial, though not exact, matching between MIBI hot spots and X-ray opacities. More than one hot spot was detected even in the smallest (0.6 cm) lesion. Post-biopsy scintigraphy showed absence of significant hot spots in two patients, whereas in the third patient one of the three hot spots was still partially present. All lesions showed cancer on histological examination. CONCLUSIONS: Measurement of radioactivity in biopsy specimens confirmed the heterogeneous distribution of radioactivity within cancers that IP had detected before biopsy.

Radioguided biopsy of osteoid osteoma: usefulness of imaging probe.

AIMS AND BACKGROUND: When removal of osteoid osteoma is performed with open biopsy, the surgeon can be guided by radioactivity of 99mTc-MDP (methylene D- phosphonate) acquired by a probe. MATERIAL AND METHODS: We compared the performance of a commercially available ZnCdTe probe (Neoprobe 2000) and a one-square-inch-field-of-view imaging probe (IP) on two patients undergoing open biopsy for osteoid osteoma. Triphasic bone scintigraphy was performed before operation and Neoprobe as well as IP were used in the operating room by two nuclear physicians. When the surgeon asked for guidance, each nuclear physician had to indicate a precise direction. RESULTS: The surgeon asked for guidance once in the first operation, on a patient with osteoid osteoma of the femur, and four times in the second operation, for osteoid osteoma of the acetabulum. The indications provided by IP were correct 5/5 times, whereas the commercial probe was correct 3/5 times. Both devices were able to assess the surgical radicality. After biopsy, bone samples were divided into high-count and low-count samples. Pathological examination confirmed the presence of osteoid osteoma in high-count samples. CONCLUSIONS: IP has already been used to guide biopsy, but only in breast disease. The present work confirmed its good performance also in orthopedics as a portable mini gamma camera that can be used in the operating room.

Sentinel node detection with imaging probe.

A once-square-inch-field-of-view mini gamma camera, whose first prototype was built by us in 1998 and given the name imaging probe (IP), was initially employed in sentinel lymph node (SLN) detection. This is probably the best way of learning how to use it. In the present work IP was used for SLN localization by a medical team that, after having been trained by the group of nuclear physicians of "La Sapienza" University who designed and first used the detector, used IP at their own hospital to 1) acquire experience for future use during surgery (a cooperative project on IP-radioguided orthopedic surgery is ongoing) and 2) start multicenter trials with IP. The SLN was identified and localized with IP and a non-imaging probe, Neoprobe 2000, in six patients with breast cancer who underwent lymphoscintigraphy for SLN biopsy. The operators who used Neoprobe and IP were blinded to each other's findings and to the results obtained with the large-field-of-view Anger camera that was used for lymphoscintigraphy. The Anger camera, IP and Neoprobe detected seven SLNs in six patients. The mean detection time was 2 mins 6 s (standard deviation (SD) 26 s) with IP, and 2 mins 18 s (SD 47 s) with Neoprobe 2000. The SLN that was most difficult to find was detected in 2 mins 56 s with IP and 3 mins 45 s with Neoprobe. The operators' subjective impression of having detected the SLN was "absolutely sure" for 7/7 nodes with IP and "absolutely sure" for 5/7 nodes with Neoprobe.

Intraoperative sentinel node detection by an innovative imaging probe.

Intraoperative tumor detection has been used in many applications, and today the sentinel node technique is a widely employed surgical procedure in breast cancer. Different detector systems are employed but several problems have been reported in clinical practice, in particular the difficulty to accurately detect the sentinel node within the axillary soft tissue. The problem is even greater for abdominal and thoracic tumors. We propose an innovative Imaging Probe (IP) able to visualize on a monitor the primary tumor and secondary lesions if appropriately radiolabeled. The IP can be optimally applied for minimally invasive surgery in breast cancer treatment, and a preliminary experience related to 15 patients and 20 sentinel nodes is reported here. We compared the results obtained with the IP to those obtained with an Anger camera and a traditional scintillation detector, and found them to be very promising. In particular the surgeon's work is greatly facilitated by direct visual guidance instead of a generic acoustic signal.

Detection of sentinel node in breast cancer: pilot study with the imaging probe.

The commonly used gamma probes are easy to use but also give rough information when employed in radioisotope-guided surgery. When images are required for exact localization, a gamma camera as well as a probe have to be used. Position-sensitive photomultipliers have contemporaneously allowed high-resolution scintigraphy and miniaturization of gamma cameras. We have assembled a miniature gamma camera with a 1-square-inch field of view and an intrinsic resolution of about 1 mm. When the minicamera is collimated with a large-holed, highly sensitive collimator, it acquires a spatial resolution of 3 mm. This prototype has been tested in the detection of difficult-to-image breast cancer sentinel nodes. Five nodes that had not been found with the usual technique of an Anger camera plus conventional probe were checked with the miniature camera that we named imaging probe: it actually is small enough to be used as a probe and large enough to give an image. One of the five nodes was found and imaged. It was small, disease-free, close to the tumor and probably hidden by the Compton halo around the peritumoral injection site. Our pilot study shows that the imaging probe, although still a prototype, has certain advantages over conventional methods when lymph node localization is required during surgery.

High-resolution scintimammography improves the accuracy of technetium-99m methoxyisobutylisonitrile scintimammography: use of a new dedicated gamma camera.

The main disadvantage of technetium-99m methoxyisobutylisonitrile (MIBI) prone scintimammography is its limited sensitivity for T1a and T1b cancers with a size of less than 1 cm. We have developed a high-resolution scintimammographic technique using a gamma camera based on a new concept, namely a position-sensitive photo-multiplier tube. The field of view of this camera, previously known as the SPEM (single photon emission mammography) camera, was 10 cm diameter. Scintimammographic images were acquired in the axial view; each breast was compressed to a thickness of 3-6 cm, modal class 4 cm. When the compressed breast was larger than the field of view, more than one study was performed in order to image the entire gland. Fifty-three patients were studied with high-resolution-scintimammography (HRSM) and Anger camera prone scintimammography (ACPSM). HRSM was performed 70 min after i.v. administration of 740 Mbq of (99m)Tc-MIBI; ACPSM images were acquired 10 and 60 min following the injection. Early 10-min ACPSM images were only evaluated for routine diagnostic purposes, while comparison was carried out between the 60-min ACPSM and 70-min HRSM images. At fine-needle aspiration (FNA) and/or open biopsy, 31 patients showed cancer: 15 T1c, 11 T1b and 5 T1a. In T1a-T1b cancers, the sensitivity of scintimammography was 50% with ACPSM and 81.2% with HRSM (P<0.01). Specificity was 86% with both techniques. HRSM is a promising new technique that improves the sensitivity of (99m)Tc-MIBI scintimammography in tumours sized less than 1 cm without apparently reducing its specificity. We are now working on a larger field-of-view camera.

Role of 99mTc-Sestamibi scintimammography by SPEM camera in the management of breast cancer in the elderly.

The incidence of breast cancer in the elderly is 10 fold higher than in the population younger than 65 years. Moreover, in this segment of the population there are not defined clear practice guidelines regarding patient management. X-ray mammography, the most widely used diagnostic technique, is often inadequate to differentiate benign from malignant lesions. 99mTc Sestamibi scintimammography plays an important role as complement to mammography; in fact it is a very sensitive and specific method for breast cancer detection, when cancers > 1 cm diameter are considered. However, sensitivity values fall to 50-60% in the case of small tumors (T1a and T1b). In this study we present the results of a new Small Field Of View (SFOV) Gamma Camera with very high spatial resolution that allows the first Single Photon Emission Mammography (SPEM). Eighteen patients aged 71 +/- 6 years with mammographically detected breast lesions were submitted to a Prone Scinti Mammography (PSM) by conventional Gamma Camera and to a SPEM on craniocaudal view. A final diagnosis was reached by histopathology. SPEM correctly diagnosed 15 of 16 cancers, while PSM was not able to recognize 5 malignant lesions with subcentimeter size. Both the techniques provided normal findings in the case of benign lesions. The 99mTc Sestamibi scintimammography, particularly when performed by SPEM camera, is a sensitive, specific, and non invasive method to define the nature of radiologically described breast masses and would be very useful as a complement to X-ray mammography in screening programs for breast cancer.

99mTc MIBI scintimammography with a high resolution single tube gamma camera: preliminary study.

99mTc MIBI scintimammography is a sensitive and specific diagnostic technique for breast cancer detection when cancers more than 1 cm sized are considered. However the sensitivity falls in the case of submillimetric lesions. We developed a new Small Field of View, High Resolution Detector, able to image the breast in similar conditions of x-ray mammography: it allows the performance of Single Photon Emission Mammography (SPEM) studies. Seven patients with suspicion of malignant lesions were comparatively submitted to a Prone Scintimammography (PSM) by Anger camera and to a cranio-caudal view SPEM. The final diagnosis was reached by histopathology. Four malignant lesions were identified by SPEM but not by PSM, which that failed to image two submillimetric cancers. Both the cameras gave normal findings for benign lesions, confirming the high sensitivity of this technique. The results allow us to consider the SPEM camera as promising to improve scintimammographic sensitivity, even when small-sized tumors are examined.

Single tube gamma camera for scintimammography.

The development of large area Position Sensitive Photo Multiplier Tubes (PSPMT) by Hamamatsu is opening new imaging possibilities in Nuclear Medicine. In particular the realization of the 8" PSPMT prototype represents the first important technological advantage since the discovery of the Anger Camera. PSPMT virtually integrates in one hundreds PMT allowing the creation of dedicated detectors. A Single Tube Gamma Camera based on a 5" PSPMT dedicated to scintimammography is presented and discussed in this work. To optimize gamma camera response two different scintillating arrays were tested: YAP:Ce and CsI (Tl). Their overall size cover all photocathode active area, and crystal pixel size was 2 mm x 2 mm. The detection efficiency was comparable to that of Anger Camera. The best result was obtained by CsI (Tl) scintillating: an intrinsic spatial resolution of 1.6 mm FWHM and a relative energy resolution of 17% FWHM. New image possibilities in scintimammography are offered by Single Tube Gamma Camera operating in the same radiological projection of RX mammography.

The role of Compton background and breast compression on cancer detection in scintimammography.

99mTc MIBI scintimammography is a promising diagnostic technique for cancer detection. Using a dedicated Small Field Of View Gamma Camera (SFOVGC) with the high spatial resolution recently developed, it is possible to improve the sensitivity and to achieve images in projections similar to mammography with the breast under moderate compression. This new technique is called Single Photon Emission Mammography (SPEM). Several factors affect the imaging of small cancers; breast thickness, tumor-collimator distance and body activity. A phantom study was performed to assess the role of breast compression in scintimammography. In this work we analyze the intensity and the energy distribution of Compton scattering affecting the breast scintigraphy, by a Germanium detector and by SFOVCG. Five patients with 7 to 18 mm sized cancer were studied. The intensity of Compton scattering resulted from 4 to 10 times greater than true events. The fundamental role played by breast compression to improve the scintimammographic sensitivity is discussed.

99mTc anti-D-dimer MoAb detects venous thrombi in man.

Authors' work is based on the ability of a 99mTc labelled antibody (MoAb) against D-Dimer (D-D) to visualize thrombi in man. D-Dimer is a specific epitope created during the cross-linking process of fibrin strains. Five normal volunteers and 5 patients with leg varices were given 10 mCi of 99mTc anti-D-Dimer MoAb (research approved by our Ethical Committee). Each patient gave his informed consent. Scintigraphic images were taken at 5, 60, 180 min. No adverse reaction was observed. Two patients underwent saphenous stripping 3 hrs after injection, in the other 4 patients scintigraphic images were acquired at 6 and 8 hrs. Twelve hot spots were visualized. Of these, 5 were localized during operation with a pencil-like probe and exsected. Specific activity of exsected thrombi, saphenal walls and blood samples was measured. Thrombus to vein wall ratio of 2.2 +/- 0.6 and a thrombus to blood of 3.1 +/- 0.8 was measured. In non operated patients the best scintigraphic images were obtained between 60 and 180 min. 99mTc anti-D-Dimer MoAb is a promising agent for localization of thrombi.

[Morphometric analysis of mammographic images in clinical oncology]. / L'elaborazione morfometrica di immagini mammografiche nella oncologia clinica.

The three standard projections relative to mammographies of 40 patients with breast cancer pre-operatively classified as T1-T2 were analyzed by computerized morphometric elaborations. This method si able to better define view of images, permetting pre-operative connection of staging, with an increment of 30% if confronted with histologic TNM (pTNM). The utilization of method is discussed to evaluate the best way for the local definition of tumor extension, permitting to use a correctly conservative surgery (quadrantectomy, tumorectomy) in a greater number of patients.