Toward Quantitative Small Animal Pinhole SPECT: Assessment of Quantitation Accuracy Prior to Image Compensations

Purpose  We assessed the quantitation accuracy of small animal pinhole single photon emission computed tomography (SPECT) under the current preclinical settings, where image compensations are not routinely applied. Procedures  The effects of several common image-degrading factors and imaging parameters on quantitation accuracy were evaluated using Monte-Carlo simulation methods. Typical preclinical imaging configurations were modeled, and quantitative analyses were performed based on image reconstructions without compensating for attenuation, scatter, and limited system resolution. Results  Using mouse-sized phantom studies as examples, attenuation effects alone degraded quantitation accuracy by up to −18% (Tc-99m or In-111) or −41% (I-125). The inclusion of scatter effects changed the above numbers to −12% (Tc-99m or In-111) and −21% (I-125), respectively, indicating the significance of scatter in quantitative I-125 imaging. Region-of-interest (ROI) definitions have greater impacts on regional quantitation accuracy for small sphere sources as compared to attenuation and scatter effects. For the same ROI, SPECT acquisitions using pinhole apertures of different sizes could significantly affect the outcome, whereas the use of different radii-of-rotation yielded negligible differences in quantitation accuracy for the imaging configurations simulated. Conclusions  We have systematically quantified the influence of several factors affecting the quantitation accuracy of small animal pinhole SPECT. In order to consistently achieve accurate quantitation within 5% of the truth, comprehensive image compensation methods are needed. Significance: We assessed the quantitation accuracy of small animal pinhole SPECT, providing reference information for the current preclinical studies.     

A systematic analysis of factors which may impact upon tomographic perfusion imaging measurements: Implications for the use of Tc-99m sestamibi in acute myocardial infarction

Background: The use of acute Tc-99m sestamibi imaging has provided a valuable methodology to assess myocardium at risk and collateral blood flow. Objective: The purpose of this study was to determine the impact of physical, physiologic, and reconstruction factors on the extent and severity of Tc-99m sestamibi images in a porcine model of coronary occlusion and reperfusion. Methods and results: Eleven pigs underwent 40 min of coronary occlusion using a balloon catheter followed by reperfusion. Radiolabeled microspheres were injected during occlusion for blood flow determination and 20–30 mCi of Tc-99m sestamibi was injected intravenously for cardiac imaging. Each animal underwent four modes of gamma camera imaging: a cardiac and respiratory gated SPECT study, an ungated SPECT study, a post-mortem SPECT study and an ex-situ study where the heart was sliced into five short axis slices and directly imaged. All animals had extensive wall motion abnormalities at the time of imaging. Myocardial risk area by ex-situ imaging was 32 ± 9% LV and did not significantly change with the addition of a chest cavity and tomographic reconstruction (post-mortem and gated imaging) or cardiac and respiratory motion (ungated imaging). Defect severity was significantly underestimated with the addition of a chest cavity and tomographic reconstruction but was unaltered by cardiac and respiratory motion. Conclusions: The assessment of risk area acutely by SPECT Tc-99m sestamibi imaging is unaffected by cardiac motion obviating the necessity for gated imaging. Estimated defect severity (which has been used as a measure of collateral flow) is significantly reduced by the chest wall and tomographic acquisition and reconstruction suggesting a role for scatter and attenuation algorithms for this measure.     

Tc-99m MIBI uptake in traumatic vertebral fractures and metastatic vertebral lesions: Comparison with Tc-99m MDP

This study compared technetium-99m-hexakis-2-methoxyisobutyl-isonitrile (Tc-99m MIBI) with technetium-99m methylene diphosphonate (Tc-99m MDP) to determine whether Tc-99m MIBI could distinguish vertebral metastases from traumatic vertebral fractures. Twenty patients with traumatic vertebral fracture (and no malignant disease) and 14 patients with metastatic vertebral lesions were evaluated. Three to 4 hours after intravenous injection of Tc-99m MDP, images of the vertebrae in all patients were obtained. Corresponding Tc-99m MIBI images were acquired within 4 days after the Tc-99m MDP bone images were obtained. Computed tomography and magnetic resonance imaging demonstrated 24 vertebral traumatic fractures and 44 vertebral metastases. On conventional bone scans, Tc-99m MDP activity was increased in 92% of vertebral fractures and in 100% of vertebral metastases. However, on MIBI scans, no abnormal findings were observed in the vertebrae with fracture, although increased activity was seen in 73% of vertebral metastases. In this study, traumatic vertebral fractures tended to display no pathologic increases in Tc-99m MIBI uptake, whereas bone metastases usually appeared with high uptake. In light of the excellent specificity of Tc-99m MIBI scans compared with Tc-99m MDP bone scans, imaging studies that use Tc-99m MIBI scans may play an important complementary role in differentiating vertebral metastases from traumatic vertebral fractures.     

Intrapatient Comparison of 2-Deoxy-2-[F-18]fluoro-<Emphasis Type="SmallCaps">d</Emphasis>-glucose with Positron EmissionTomography/Computed Tomography to Tc-99m Fanolesomab (NeutroSpec) for Localization of Infection

Purpose This study evaluated the efficacy of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) with positron emission tomography/computed tomography (PET/CT) in comparison with Tc-99m fanolesomab (NeutroSpec) for imaging infection. Procedures Twelve patients with possible infection were studied with both FDG-PET/CT and Tc-99m fanolesomab. One patient was studied twice for a total of 13 paired studies. The final determination of the presence or absence of infection and the site(s) of infection at the time of imaging was made by an infectious disease physician using culture results and other relevant information. The sensitivity, specificity, and accuracy were calculated for each imaging study on a per paired study basis and a per lesion basis. In addition, the quality of lesion depicted was compared between the two studies. Results Three patients were determined not to have infection. Ten paired studies, in nine patients, were determined to have one or more sites of infection: seven had one site and three had two sites. On a per paired study basis the sensitivity, specificity, and accuracy of FDG-PET/CT were all 100%; for Tc-99m fanolesomab these parameters were 30, 100, and 46%, respectively (P < 0.01 for sensitivity and accuracy). On a per site basis the results for FDG-PET/CT were all 100% and for Tc-99m fanolesomab they were 23, 100, and 38% (P < 0.01 for sensitivity and accuracy). In the three sites of infection shown by both studies, FDG-PET/CT was judged to be superior in spatial resolution and anatomic localization compared to Tc-99m fanolesomab in all three sites. Conclusion FDG-PET/CT is superior to Tc-99m fanolesomab for detecting and localizing sites of infection.     

Localization of (99m)Tc-Labeled ApoB Synthetic Peptide in Arterial Lesions of an Experimental Model of Spontaneous Atherosclerosis

We have previously shown that after administration of (123)I-SP-4 (a synthetic ApoB peptide fragment) to Watanabe heritable hyperlipidemic (WHHL) rabbits that foci of tracer uptake can be identified by external gamma camera imaging which correspond to regions of the aortas found to contain abundant atherosclerotic lesions at postmortem evaluation. Because (99m)Tc is preferred over (123)I for scintigraphic imaging, we prepared a (99m)Tc-labeled form of the SP-4 peptide, designated (99m)Tc-P199. To assess the feasibility of detecting atherosclerotic lesions using (99m)Tc-P199 and to compare the relative uptake of the (99m)Tc-labeled and radioiodinated peptides by such lesions, an admixture of (99m)Tc-199 and (125)I-SP-4 was administered to 11 WHHL and 2 normal rabbits. These animals were imaged for up to 3 h and were sacrificed 3--4 h after injection. The extent of aortic lesion involvement and radiotracer uptake were quantitatively compared by planimetric analysis of photographs of the endothelial surface, (99m)Tc-P199 ex vivo images and (125)I-SP-4 autoradiograms of the excised aortas. Pairwise correlation coefficients for planimetric analysis were as follows: photographs versus ex vivo images, r = 0.83, p = 0.003; photographs versus autoradiograms, r = 0.87, p = 0.001; ex vivo images versus autoradiograms, r = 0.83, p = 0.003. (99m)Tc-199 in vivo gamma camera images revealed relatively weak focal aortic uptake in 8 of 11 WHHL rabbits manifesting aortic lesions, and focal carotid artery uptake in 4 of 6 WHHL rabbits manifesting carotid lesions. Neither aortic nor carotid foci were visualized in the normal rabbits. We conclude that (99m)Tc-199 localizes specifically in atherosclerotic lesions and may be useful for external imaging of atherosclerosis.     

Should imaging at stress always be followed by imaging at rest in Tc-99m MIBI SPECT?

Objectives. We addressed the question whether in patients with cardiac chest pain referred for stress myocardial perfusion scintigraphy, Tc-99m MIBI SPECT stress imaging should always be followed by a rest imaging procedure. Background. Using Tc-99m MIBI imaging a stress-rest sequence is usually performed implying that the resting study always follows the stress study irrespective of the results of the stress study. As a normal stress study would eliminate a subsequent resting study, it appears desirable to potentially define certain subsets of patients in whom a normal stress study can be expected in order to determine a more selective referral approach to the nuclear medicine department. The consequences of such a more streamlined approach would less impose on the logistics of the department of nuclear medicine, with decrease of investigation time, radiation dose, and costs in a time of retrenchment in the medical sector. Methods. A consecutive series of 460 patients (mean age 58.2 years) was studied who were stratified to 269 patients without prior myocardial infarction, and to 191 patients with documented evidence of a previously sustained mycoardial infarction. All patients underwent Tc-99m MIBI SPECT imaging according to a two-day stress-rest protocol. Results. Patients with and without a previous myocardial infarction showed suboptimal overall predictive accuracies for the exercise electrocardiograms (58% and 60%, respectively). In the total group of 460 patients, 94 (20%) patients showed a normal stress-rest Tc-99m MIBI SPECT; this occurred in 86/269 (32%) patients without a previous myocardial infarction and in only 8/191 (4%) patients with a previous myocardial infarction. Conclusions. Patients with a stress defect at Tc-99m MIBI SPECT imaging should always undergo a resting SPECT study irrespective of the clinical and stress electrocardiographic findings. As patients without a previous myocardial infarction had a normal stress SPECT study in almost one-third (32%) of patients compared to only 4% in patients with a previous myocardial infarction, it may be useful to employ different referral and imaging strategies i.e. a stress-only versus a stress-rest procedure. To schedule referring patients differently according to the presence or absence of a previously sustained myocardial infarction may be cost-saving, less demanding for the nuclear medicine personnel, and patient-convenient. In addition, a stress-only imaging procedure reduces radiation exposure to the individual patient.     

High-resolution single-photon emission computed tomography and X-ray computed tomography imaging of Tc-99m-labeled anti-DR5 antibody in breast tumor xenografts

A murine, apoptosis-inducing monoclonal antibody (mTRA-8) targeting human DR5 was radiolabeled with Tc-99m. The binding affinity (K(d)) and the number of DR5 receptors were measured in MD MBA-231-derived 2LMP cell lines that were "sensitive" or "resistant" to mTRA-8 killing. Single-photon emission computed tomography and X-ray computed tomography (SPECT/CT) evaluated the Tc-99m-mTRA-8 retention and distribution within xenograft tumors; biodistribution analyses confirmed the levels. Scatchard assays showed specific and high binding affinity of Tc-99m-mTRA-8 to DR5; the killing efficacy of mTRA-8 was unchanged by Tc-99m labeling. There was no significant difference between sensitive and resistant 2LMP cells for K(d) values (1.5 +/- 0.3 nmol/L = acid labile), or DR5 receptors (mean/cell = 11,000). SPECT/CT imaging analyses at 6 h after injection of Tc-99m-mTRA-8 revealed the second 1.5 mm shell from the surface of the mammary fat pad tumors (n = 5; 5,627 mm(3)) retained 12.7 +/- 1.4%ID/g, higher than the other shells, with no difference between the sensitive and resistant 2LMP tumors. Binding of Tc-99m-labeled mTRA-8 in tumor was specific; excess unlabeled mTRA-8 blocked Tc-99m-mTRA-8 retention in tumor by 45%. Retention of Tc-99m-labeled isotype antibody in tumor was consistent with the blocking study, and 30% lower. These studies show that SPECT/CT imaging provided detailed distribution information of Tc-99m-labeled mTRA-8 within breast tumor xenografts. Imaging could provide a mechanism to assess DR5 modulation when DR5 therapy is combined with chemotherapy and radiation, and thereby aid in optimizing the dosing schedule.     

Tc-99m HMPAO labelled WBCs in the detection of occult sepsis in the intensive care unit

In a retrospective study involving 25 patients with occult sepsis in the ICU of Taichung Veterans General Hospital, the sensitivity and specificity of the new diagnostic method, Tc-99m HMPAO labelled white blood cells (WBCs) scan, were compared with other evaluating methods including clinical information, radiograph, ultrasound, bacterial culture, operative findings and pathological report. It was found that Tc-99m HMPAO labelled WBCs scans gave a sensitivity of 96.0%, a specificity of 84.4% and an overall accuracy of 87.3%, as well as the probable causes of false positive and false negative diagnoses were discussed. In conclusion, Tc-99m HMPAO labelled WBCs scans provide a reliable method for imaging of occult sepsis in the ICU.     

Gated SPECT imaging to detect changes in myocardial blood flow during progressive coronary occlusion

Background: The ability to track dynamic changes in myocardial blood flow (MBF) and wall motion with serial gated perfusion imaging may be a limiting factor in assessing new therapies. The purpose of this study was to determine whether gated Tc-99 m sestamibi (MIBI) SPECT imaging can track small changes in MBF in a model of progressive ischemia. Methods: Eight pigs (20 kg) underwent lateral thoracotomy for placement of an ameroid constrictor on the left circumflex coronary artery (LCX) and indwelling femoral and left atrial catheters for serial microsphere determinations of absolute MBF. Animals underwent concurrent left atrial microsphere and Tc-99 m sestamibi (0.3 mCi/Kg IV) injections at weekly intervals over 6 weeks per animal. Gated SPECT imaging was acquired for each injection using high resolution collimation and standard processing. The animals were sacrificed on day 42. Mean signal intensity (SI) from regions of interest (ROI) corresponding to control and ischemic MBF by microspheres was measured for three SPECT short-axis images. Mean contrast ratio (MCR) was calculated from the ratio of ischemic to control SI per slice. Regional wall motion (RWM) from gated images was scored 1–5 using a 16 segment model and a score index (RWMI) was calculated. Results: MBF decreased progressively (27% below resting values [P < 0.0001]) but with a clear and significant partial recovery by day 42 (13% improvement from peak ischemia, [P < 0.01]). SPECT perfusion and gated RWM closely paralleled the dynamic pattern of MBF caused by the ameroid constrictor. SPECT MCR decreased 21% from baseline scans in the LCX territory (P < 0.0001) and improved 11% from peak ischemia (P < 0.01) while the gated RWMI (1.0 at baseline) peaked at 1.36 and improved to 1.13 by day 42. Conclusion: Gated SPECT-a technique readily available-tracks dynamic changes in MBF closely with both perfusion and RWM. For trials of new therapies for the alleviation of chronic ischemia, these findings have direct implications for measuring efficacy.     

Role of nuclear medicine in the evaluation of the solitary pulmonary nodule

Tomographic imaging with either F-18 fluoro deoxyglucose (FDG) (a nonmetabolizable glucose analog that reflects tumor increased glucose metabolism) or technetium Tc-99m Depreotide (a synthetic peptide that binds with high affinity to cell surface receptors with increased expression on certain tumor cells) provides improved sensitivity and specificity in the differential diagnosis of solitary pulmonary nodules (SPN) compared with noninvasive and some invasive procedures. F-18 FDG requires instrumentation capable of coincident imaging whereas Tc-99m Depreotide can be imaged on standard gamma cameras equipped to perform single photon emission computed tomography (SPECT) imaging. Either technique performs better than CT alone, and both are cost effective on the basis of reducing unnecessary biopsies and thoracotomies in patients with negative studies indicating that the SPN is nonmalignant.     

Tc-99m-MIBI双时相显像评价甲状旁腺机能亢进症的临床研究

目的:在甲状旁腺机能亢进症患者中,评价双时相Tc-99m-MIBI甲状旁腺显像对异常甲状旁腺组织的诊断和定位。方法:35例临床检查和生化指标提示甲状旁腺机能亢进的患者,手术前1周内行双时相Tc-99m-MIBI甲状旁腺平面显像。注射740MBq的Tc-99m-MIBI,15分钟和2小时后,分别进行颈胸前位平面显像,部分病人在延迟相还进行SPECT断层显像。结果:Tc-99m-MIBI甲状旁腺显像结果与手术结果对比,双时相Tc-99m-MIBI甲状旁腺平面显像对甲状旁腺腺瘤诊断灵敏度是75%(27?36),而SPECT断层显像的灵敏度是86%(31?36);甲状旁腺增生诊断灵敏度是50%(2?4)。结论:本研究认为双时相Tc-99m-MIBI甲状旁腺显像对甲状旁腺腺瘤的诊断和定位有较高的临床价值,尤其是SPECT断层显像,而对甲状旁腺增生的诊断,有必要进行进一步研究。     

Tc-99m pyrophosphate scintigraphy for cardiac amyloidosis: concordance between planar and SPECT/CT imaging

The International Journal of Cardiovascular Imaging - The imaging protocol and the optimal cut-off points for quantitative assessment of technetium-99m pyrophosphate (Tc-99m PYP) cardiac...     

Characterization of “γ-Eye”: a Low-Cost Benchtop Mouse-Sized Gamma Camera for Dynamic and Static Imaging Studies

Purpose

Several preclinical imaging systems are commercially available, but their purchase and maintenance costs make them unaffordable for the majority of small- and medium-sized groups. Taking into account the needs of average users, we developed “γ-eye”, a mouse-sized, benchtop γ-camera suitable for in vivo scintigraphic imaging.

Procedures

The γ-eye is based on two position-sensitive photomultiplier tubes, coupled to a CsI(Na) pixelated scintillator and a low-energy lead collimator with parallel hexagonal holes.

Results

The spatial resolution of the system is 2 mm at 0 mm. The energy resolution is 26 % at 140 keV and the maximum recorded sensitivity 210 cps/MBq. The system was evaluated in a proof-of-concept animal study, using three different clinical Tc-99m-labeled radiopharmaceuticals. Phantom and animal studies demonstrate its ability to provide semiquantitative results even for short scans.

Conclusions

Systems’ performance, dimensions, and cost make γ-eye a unique solution for efficient whole-body mouse nuclear imaging.

     

On-site preparation of technetium-99m labeled human serum albumin for clinical application

Technetium-99m labeled human serum albumin (Tc-99m HSA) is an important radiopharmaceutical for clinical applications, such as cardiac function tests or protein-losing gastroenteropathy assessment. However, because of transfusion-induced infectious diseases, the safety of serum products is a serious concern. In this context, serum products acquired from patients themselves are the most ideal tracer. However, the development of rapid separation and easy clinical labeling methods is not yet well established. Under such situation, products from the same ethnic group or country are now recommended by the World Health Organization as an alternative preparation. This article describes the on-site preparation of Tc-99m HSA from locally supplied serum products. Different formulations were prepared and the labeling efficiency and stability were examined. Radio-labeling efficiencies were more than 90% in all preparation protocols, except for one that omitted the stannous solution. The most cost-effective protocol contained HSA 0.1 mg, treated with stannous fluoride 0.2 mg, and mixed with Tc-99m pertechnetate 30 mCi. A biodistribution study was performed in rats using a gamma camera immediately after intravenous administration of radiolabeled HSA. Tissue/organ uptake was obtained by measuring the radioactivity in organs after sacrificing the rats at timed intervals. The biologic half-life was about 32 min, determined from sequential venous blood collections. These data indicate that our preparation of Tc-99m HSA is useful and potentially applicable clinically. In addition, this on-site preparation provides the possibility of labeling a patient's own serum for subsequent clinical application.     

Preliminary evaluation in humans of Tc-99m-Q3, a new tracer for myocardial perfusion imaging

Trans[99m-Tc-acac₂en(TMPP)₂]⁺, where acac₂en is N,N′-ethylenebis(acetylacetone iminate) and TMPP is tris-(3 methoxy propyl) phosphine, (shortened Q3) is a new lipophilic Technetium-99m-labelled compound developed for myocardial perfusion imaging. Encouraging data were obtained in the experimental animal. Aim of this study was to perform a preliminary evaluation of Q3 imaging in humans and to compare it with a reference coronary flow tracer such as Tc-99m microspheres. Eight coronary artery disease patients (males, age 58.5±10 years) were studied. They were injected with 740 MBq of Q3 and single photon emission computed tomography (SPECT) was performed 90 minutes later. After 3 days 740 MBq of Tc-99m microspheres were injected through a pig-tail catheter in the left ventricle (LV), during heart catheterization, and SPECT was acquired 60 minutes later. Q3 images showed a good target/background activity ratio: LV wall/LV cavity=4.16±1.2; myocardium/ lung=3.95±0.52; the related values with microspheres were 6.36±2.48 (N.S.) and 4.57±1.07 (N.S.), respectively. Q3 was cleared by the liver and at the moment of SPECT collection the myocardium/liver activity ratio was 1.54±0.32. The Q3 LV lateral wall/septum activity ratio showed a good correlation with the corresponding microspheres ratio: Q3 ratio=0.027 + 0.95 microspheres ratio, r=0.89, SEE=1.12, p<0.005. In conclusion Q3 seems to have a potential value as myocardial perfusion tracer in humans, even if at present the labelling procedure is extremely laborious.     

SPECT Imaging of Muscle Injury with [99mTc]MDP in a Mouse Model of Muscular Dystrophy

Molecular Imaging and Biology - Tc-99m methylene diphosphonate ([99mTc]MDP) is an in vivo bone imaging agent that also accumulates in injured skeletal muscle cells. The objective of this study was...     

Exanthema after a stress Tc‐99m sestamibi study: continue with a rest sestamibi study?

Purpose: A mild allergic reaction assumed to be caused by injection of Tc-99m sestamibi for a stress myocardial perfusion imaging (MPI) is presented. We want to discuss the risk involved in completing the MPI with another sestamibi injection, and the precautions and possible treatment in case of a further reaction. Material and methods: A patient experienced a maculo-papular exanthema, i.e. a mild, probably allergic, adverse event (AE) after a stress MPI including administration of a dose of Tc-99m sestamibi. A rest MPI was needed to decide whether coronary bypass surgery should be performed. After prophylactic treatment with antihistamine and corticosteroid, an uneventful rest MPI was performed. Discussion and conclusion: International recommendations or guidelines related to treatment of AEs after nuclear medicine studies do not exist. Serious AEs in nuclear medicine are very rare, but anaphylactic reactions have been reported and may be life threatening. If repeated administration of the radio-pharmaceutical must be given, the prophylactic and therapeutic interventions should follow general international guidelines for allergic reactions.     

Solitary Splenic Lesions

Solitary splenic lesions are unusual. A differential diagnosis can be organized around their basic imaging appearance as either predominantly cystic or solid. Other imaging characteristics, including vascular enhancement and activity on Tc-99m sulfur colloid scan, as well as clinical history may narrow the diagnostic possibilities. Cystic lesions include post-traumatic, inflammatory and infectious pseudocysts, congenital cysts, lymphangiomas and cystic metastasis. Solid lesions include both nonneoplastic lesions such as splenic hamartoma, benign tumors such as hemangioma and malignant masses including lymphoma and angiosarcoma. Percutaneous biopsy may be used for histologic diagnosis when required.     

Role of99mTc-IDA cholescintigraphy in evaluating biliary tract disorders

Technetium-99m IDA cholescintigraphy has provided a new, noninvasive means of visualizing biliary tract function. It has become the procedure of choice in patients with suspected acute cholecystitis because of its ability to most accurately detect functional obstruction or patency of the cystic duct as opposed to ultrasound's ability to detect only anatomic changes such as the presence of calculi or a thickened gallbladder wall. These latter findings are more important in establishing the diagnosis of chronic cholecystitis where ultrasound shares a position of prime importance with the oral cholecystogram. Tc-99m IDA cholescintigraphy has also been particularly useful in evaluating bile leaks, biliary-enteric anastomosis patency and the post-cholecystectomy patient with recurrent pain. In the patient with cholestasis, ultrasound is usually the procedure of choice since it establishes whether or not ductal dilatation is present and frequently can determine the cause of obstruction. Cholescintigraphy has played an ancillary role in many cases by demonstrating the level of partial obstruction, but it does not have the anatomic resolution to visualize the cause of obstruction. Occasionally, in the evaluation of cholestasis, cholescintigraphy has proven to be the only modality which has identified the presence of acute common duct obstruction or localized intrahepatic ductal obstruction. All in all, Tc-99m IDA cholescintigraphy has had a dramatic impact upon hepatobiliary diagnosis.     

A new ultrasound instrument for in vivo microimaging of mice

We report here on the design and evaluation of the first high-frequency ultrasound (US) imaging system specifically designed for microimaging of the mouse. High-frequency US or US biomicroscopy (UBM) has the advantage of low cost, rapid imaging speed, portability and high resolution. In combination with the ability to provide functional information on blood flow, UBM provides a powerful method for the investigation of development and disease models. The new UBM imaging system is demonstrated for mouse development from day 5.5 of embryogenesis through to the adult mouse. At a frequency of 40 MHz, the resolution voxel of the new mouse scanner measures 57 microm x 57 microm x 40 microm. Duplex Doppler provides blood velocity sensitivity to the mm per s range, consistent with flow in the microcirculation, and can readily detect blood flow in the embryonic mouse heart, aorta, liver and placenta. Noninvasive UBM assessment of development shows striking similarity to invasive atlases of mouse anatomy. The most detailed noninvasive in vivo images of mouse embryonic development achieved using any imaging method are presented.