Use of ultrasound-guided autologous bone marrow transfer for treatment of suspensory ligament desmitis in 30 race horses (2003-2010).

OBJECTIVE: To evaluate the racing performance of horses that underwent ultrasound-guided intralesional injection of autologous bone marrow aspirate for treatment of selected forelimb suspensory ligament (body or branch) core lesions. DESIGN: Retrospective cohort study of 13 Standardbred and 17 Thoroughbred race horses. METHODS: Autologous bone marrow aspirated from the sternebrae was injected, under ultrasound guidance, into suspensory ligament core lesions (body or branch). Racing records were reviewed for a comparison of performance before and after surgery. RESULTS: Of the 13 Standardbreds, 9 (69%) had one or more starts within the follow-up period and 9 (69%) had five or more starts. Of the 17 Thoroughbreds, 15 (88%) had one or more starts within the follow-up period and 12 (71%) had five or more starts. Eight Standardbred horses had at least one start both before and after surgery. Earnings per start did not differ significantly between the three starts immediately after surgery compared with the three starts immediately prior to surgery. Thirteen Thoroughbred horses had at least one start both before and after surgery. Earnings per start were less for the three starts immediately after surgery compared with the three starts immediately prior to surgery. CONCLUSIONS AND CLINICAL RELEVANCE: A horse with a core lesion in the branch or body of the suspensory ligament has a good prognosis for return to racing after treatment with intralesional injection of bone marrow aspirate.

Enhanced homing permeability and retention of bone marrow stromal cells by noninvasive pulsed focused ultrasound.

Bone marrow stromal cells (BMSCs) have shown significant promise in the treatment of disease, but their therapeutic efficacy is often limited by inefficient homing of systemically administered cells, which results in low number of cells accumulating at sites of pathology. BMSC home to areas of inflammation where local expression of integrins and chemokine gradients is present. We demonstrated that nondestructive pulsed focused ultrasound (pFUS) exposures that emphasize the mechanical effects of ultrasound-tissue interactions induced local and transient elevations of chemoattractants (i.e., cytokines, integrins, and growth factors) in the murine kidney. pFUS-induced upregulation of cytokines occurred through approximately 1 day post-treatment and returned to contralateral kidney levels by day 3. This window of significant increases in cytokine expression was accompanied by local increases of other trophic factors and integrins that have been shown to promote BMSC homing. When BMSCs were intravenously administered following pFUS treatment to a single kidney, enhanced homing, permeability, and retention of BMSC was observed in the treated kidney versus the contralateral kidney. Histological analysis revealed up to eight times more BMSC in the peritubular regions of the treated kidneys on days 1 and 3 post-treatment. Furthermore, cytokine levels in pFUS-treated kidneys following BMSC administration were found to be similar to controls, suggesting modulation of cytokine levels by BMSC. pFUS could potentially improve cell-based therapies as a noninvasive modality to target homing by establishing local chemoattractant gradients and increasing expression of integrins to enhance tropism of cells toward treated tissues.

Biodistribution of bone marrow mononuclear cells in chronic chagasic cardiomyopathy after intracoronary injection.

BACKGROUND: Animal and human clinical studies have indicated that bone marrow (BM) mononuclear cell (MNC) therapy for Chagasic Cardiomyopathy (ChC) is feasible, safe and potentially efficacious. Nevertheless, little is known about the retention of these cells after intracoronary (IC) infusion. METHODS: Our study investigated the homing of technetium-99m ((99m)Tc) labeled BM MNCs and compared it to thallium-201 ((201)Tl) myocardial perfusion images using the standard 17-segment model. Six patients with congestive heart failure of chagasic etiology were included. RESULTS: Scintigraphic images revealed an uptake of 5.4%±1.7, 4.3%±1.5 and 2.3%±0.6 of the total infused radioactivity in the heart after 1, 3 and 24h, respectively. The remaining activity was distributed mainly to the liver and spleen. Of 102 segments analyzed, homing took place in 36%. Segments with perfusion had greater homing (58.6%) than those with decreased or no perfusion (6.8%), p<0.0001. There was no correlation between the number of injected cells and the number of segments with homing for each patient (r=-0.172, p=0.774). CONCLUSIONS: These results indicate that (99m)Tc-BM MNCs delivered by IC injection homed to the chagasic myocardium. However, cell biodistribution was heterogeneous and limited, being strongly associated with the myocardial perfusion pattern at rest. These initial data suggest that the IC route may present limitations in chagasic patients and that alternative routes of cell administration may be necessary.

Quantitative ultrasound detects bone changes following bone marrow transplantation in pediatric subjects with hematological diseases: a longitudinal study.

BACKGROUND: Bone marrow transplantation (BMT) is associated with bone morbidity. We investigated bone status with quantitative ultrasound (QUS) in pediatric patients with hematological diseases prior to and up to 3 yr following BMT. METHODS: Phalangeal QUS measures for amplitude- dependent speed of sound (Ad-SoS) and bone transmission time (BTT) were obtained in 40 hematological patients (25 with malignant, 15 with non-malignant disease; 9.7+/-4.9 yr) before BMT and 6, 12, 24, and 36 months after BMT. Bone parameters were expressed as Z-scores based on age-sex-matched normal controls. RESULTS: Mean Ad-SoS and BTT Z-scores were normal before BMT and reduced at 36 months (analysis of variance: p=0.0542 and p=0.0233). Ad-SoS and BTT Z-scores remained relatively stable in the first 6 months after BMT and then progressively decreased reaching a plateau at 12-36 months. In non-malignant patients, BTT Z-score decreased at 6-12 months (p=0.029) and subsequently increased, while in malignant patients BTT Z-score showed a decrease at 12-24 months. Pre-pubertal subjects displayed a drop of BTT Z-Score values at both 12 (p=0.023) and 36 months after BMT (p=0.049), while BTT Z-score remained relatively unchanged in pubertal subjects. Early impairment of BTT Z-score was found in patients who suffered acute graft versus host disease (GVHD) compared to patients without this clinical condition; BTT Z-score was lower at 36 months (p=0.045). CONCLUSIONS: Longitudinal assessment by QUS of pediatric BMT survivors evidenced that bone status is mildly affected up to 36 months after BMT, mainly in malignant patients, in pre-pubertal subjects at BMT and in patients who suffered acute GVHD.

Imaging the lungs in patients treated for lymphoma.

The lymphomas are a heterogeneous group of malignancies, which exhibit a range of different molecular features, genetics, and clinical presentations. Consequently, therapeutic approaches and clinical outcomes differ greatly. Following therapy, the thorax may be a site of disease recurrence, but infection, drug reactions, and radiation pneumonitis are commonly encountered. We present a comprehensive review of these conditions, focussing on their radiological appearances, in order that radiologists may better engage their colleagues in haemato-oncology.

Individual differences in the effectiveness of intracoronary bone marrow cell transplantation assessed by gated sestamibi SPECT/FDG PET imaging.

BACKGROUND: The impact of different levels of tracer uptake on improvements of left-ventricular (LV) function was analyzed in patients treated by intracoronary bone marrow cell (BMC) transplantation. METHODS AND RESULTS: Thirty-one patients with irreversible damage after their first acute myocardial infarction (MI), as confirmed by sestamibi single-photon emission computed tomography (MIBI SPECT)/fluorodeoxyglucose positron emission tomography (FDG PET), underwent high-dose (1 x 10(8) cells) BMC transplantation, whereas 31 similar patients were randomly integrated into a control group. In 11 BMC-treated patients with very low sestamibi uptake at less than 30% of maximum in the infarcted area, the mean left-ventricular ejection fraction (LVEF) improved after 3 months of follow-up by 3% only, and mean end-diastolic/end-systolic volumes (EDV/ESV) enlarged by 10/1 mL (P = NS vs controls). In 20 BMC-treated patients with higher sestamibi uptake in the range of 31% to 50% of maximum, LVEF improved by 7%, and EDV/ESV decreased by 5/12 mL (P < .05 vs BMC-treated subgroup with low MIBI uptake and controls). No similar categorization was seen in the control group: in patients with higher sestamibi uptake or very low uptake, the LVEF increased by 2% and 3% only, and the EDV/ESV enlarged in both subgroups by 12/4 mL and 12/2 mL, respectively (P = NS). CONCLUSIONS: Our results suggest the capability of SPECT/PET imaging to select patients who will receive the maximum benefit from BMC therapy.

The central nervous system complications of bone marrow transplantation in children.

Bone marrow transplantation (BMT) is widely performed for both neoplastic and non-neoplastic disease. Before BMT, patients are prepared with high-dose chemotherapy, frequently associated with total-body radiation, to destroy residual malignant cells and to reduce immunologic resistance. BMT is associated with several central nervous system (CNS) complications secondary to underlying disease, prolonged myelosuppression, and the use of immunosuppressive drugs. These complications include infections, vascular disease, drug-induced neurotoxicity, metabolic disturbance, and post-BMT carcinogenesis. The immune status of children after BMT can be divided into three phases: the pre-engraftment period (days 0-30 after BMT), the post-engraftment period (days 30-100), and the late phase (after day 100). The timing of CNS complications that occur after BMT, as for complications in other organs, can be described with reference to these three phases of immune status. It is essential that radiologists become familiar with the relationships between the immune status of the recipient and the times of onset of these disorders, and with the neuroimaging patterns associated with the various complications. CNS complications can be life-threatening for immunosuppressed children, so accurate diagnosis is important for prompt and appropriate treatment.

Dental implant treatment with different techniques for sinus floor elevation--a case report.

A 60-year-old man with missing maxillary molar teeth received dental implant therapy for reconstruction of occlusion. Sinus floor elevation with autogenous bone graft consisting of iliac bone block and particulate cancellous bone and marrow (PCBM) was performed in the bilateral maxillary sinuses for implant placement. On the right side, bone height in the molar region was less than 2mm. Therefore, a delayed protocol was applied, and 2 implants were placed 4 months after bone grafting. Bone graft resorption occurred during the healing period of 4 months. On the left side, 3 implants were placed simultaneously with sinus floor elevation, as bone height in the molar region was more than 4-5mm. The bone graft was carried out at the same time as implant placement. After implant placement, resorption of the bone graft stopped, and the superstructures were delivered on both sides. The tissues around the implants were clinically healthy at one year after examination. Sinus floor elevation with autogenous bone graft is an acceptable option for implant treatment in the maxillary molar region where there is adequate height of existing bone. In postoperative care, it is important to undertake adequate follow-up to ascertain occurrence of bone graft resorption.

Imaging the complications of bone marrow transplantation in children.

Bone marrow transplantation is frequently performed to restore hematologic and immunologic competence after chemotherapy and radiation therapy for a range of childhood malignancies, as well as to treat various congenital conditions in which hematologic and immunologic functions are depressed or absent. Potentially devastating complications may occur during the pre-engraftment period after bone marrow transplantation, when marrow aplasia may supervene for several weeks until engraftment occurs, as well as during the post-engraftment period (the 3 months after engraftment) and in subsequent months and years. Complications of bone marrow transplantation may be classified either according to the time interval between transplantation and the occurrence of the complication or according to the organ system affected. The range of complications that may affect the central nervous system and the rest of the body may be detected with ultrasonography, computed tomography, and magnetic resonance imaging. Neurologic, paranasal sinus, pulmonary, and abdominopelvic complications all may be seen after bone marrow transplantation. Graft-versus-host disease and lymphoproliferative disorders also may occur. The increasing use of bone marrow transplantation mandates that the radiologist be familiar with the full range of potential complications and their imaging appearances.

Cell therapy in murine atherosclerosis: in vivo imaging with high-resolution helical SPECT.

PURPOSE: To determine the feasibility of in vivo localization and quantification of indium 111 (111In)-oxine-labeled bone marrow (BM) with high-resolution whole-body helical single photon emission computed tomography (SPECT) in an established murine model of atherosclerosis and vascular repair. MATERIALS AND METHODS: The institutional animal care and use committee approved this study. BM from young B6 Rosa 26 Lac Z+/+ mice was radiolabeled with 111In-oxine. On days 1, 4, and 7 after administration of radiolabeled cells, five C57/BL6 apolipoprotein E-deficient mice and five wild-type (WT) control mice were imaged with whole-body high-resolution helical SPECT. Quantification with SPECT was compared with ex vivo analysis by means of gamma counting. Autoradiography and beta-galactosidase staining were used to verify donor cell biodistribution. Linear regression was used to assess the correlation between continuous variables. Two-tailed Student t test was used to compare values between groups, and paired two-tailed t test was used to assess changes within subjects at different time points. RESULTS: SPECT image contrast was high, with clear visualization of BM, liver, and spleen 7 days after administration of radiolabeled cells. SPECT revealed that 42% and 58% more activity was localized to the aorta and BM (P<.05 for both), respectively, in apolipoprotein E-deficient mice versus WT mice. Furthermore, 28% and 27% less activity was localized to the liver and spleen (P<.05 for both), respectively, in apolipoprotein E-deficient mice versus WT mice. SPECT and organ gamma counts showed good quantitative correlation (r=0.9). beta-Galactosidase staining and microautoradiography of recipient aortas showed donor cell localization to the intima of visible atherosclerotic plaque but not to unaffected regions of the vessel wall. CONCLUSION: High-resolution in vivo helical pinhole SPECT can be used to monitor and quantify early biodistribution of 111In-oxine-labeled BM in a murine model of progenitor cell therapy for atherosclerosis.

Detection of 111In-oxine-labeled bone marrow stromal cells after intravenous or intralesional administration in chronic paraplegic rats.

Recent studies suggested that bone marrow stromal cells (BMSC) may have a therapeutic role in the treatment of paraplegia secondary to severe spinal cord injury (SCI). For this reason, we have studied the possibility of using nuclear medicine imaging techniques to evaluate the permanency and migration of BMSC after transplantation procedures in chronic paraplegic Wistar rats. After intravenous administration of 111In-oxine-labeled BMSC, gammagraphic images showed that the activity distributed all over the organism, but in the spinal cord only scarce activity was identified. When 111In-oxine-labeled BMSC were injected within the traumatic centromedullary cavity of paraplegic animals, the gammagraphic images showed persistent activity in the lesion zone, without any activity migrating to the rest of the organism, at least during the whole time of the study (10 days after transplantation procedures). Our results show the utility of 111In labeling for to know the permanency and distribution of BMSC after grafting procedures, and suggest the convenience of the intralesional administration of BMSC, instead of the intravenous administration, in the treatment of chronic traumatic paraplegia.

Targeted bone marrow radioablation with 153Samarium-lexidronam promotes allogeneic hematopoietic chimerism and donor-specific immunologic hyporesponsiveness.

BACKGROUND: Transplantation tolerance, defined as acceptance of a graft by an otherwise fully immunocompetent host, has been an elusive goal. Although robust tolerance has been achieved by the induction of stable hematopoietic chimerism after bone marrow transplantation, lethal or sublethal radiation conditioning used to induce long-term chimerism precludes its clinical use. We studied whether targeted delivery of radiation to bone marrow could allow for bone marrow cell (BMC) engraftment, chimerism, and donor-specific tolerance in the absence of the side effects associated with external irradiation. METHODS: We administered a radioactive bone-seeking compound (Samarium-Lexidronam, Quadramet, Berlex Laboratories, Wayne, NJ) together with transient T-cell costimulatory blockade to recipient mice. Allogeneic BMCs were given 7 or 14 days after preconditioning. Costimulatory blockade was obtained by the use of an anti-CD154 antibody for 4 weeks. Chimerism was assessed by flow cytometry. Mice then received donor-specific and third-party skin grafts. Graft survival was analyzed with mechanisms of donor-specific hyporesponsiveness. RESULTS: High levels of stable chimerism across an allogeneic barrier were achieved in mice by a single administration of Samarium-Lexidronam, transient T-cell costimulatory blockade, and BMC transplantation. A large percentage of chimeric animals retained donor-derived skin grafts for more than 120 days without requiring additional immunosuppression, suggesting that harsh cytotoxic preconditioning is not necessary to achieve stable chimerism and donor specific hyporesponsiveness. Analysis of the T-cell repertoire in chimeras indicates T-cell deletional mechanisms. CONCLUSIONS: These data broaden the potential use of BMC transplantation for tolerance induction and argue for its potential in treating autoimmune diseases.

Pulmonary complications in bone marrow transplantation.

This article reviews the most common pulmonary complications after bone marrow transplantation (BMT) and their radiologic presentations. An approach emphasizing the common complications that occur in relation to the immunosuppression recovery timeline is presented. An update on newer techniques of marrow transplantation and preparatory regimen drugs will be discussed. These newer techniques may have an effect on the radiologic appearance of some BMT complications. The diagnostic approach, management, and some evolving therapies of BMT patients with pulmonary complications will also be discussed.

Osteonecrosis of the femoral head after allogeneic bone marrow transplantation.

A comparative retrospective analysis of 100 consecutive patients after bone marrow transplantation was performed with magnetic resonance imaging in addition to plain radiography for the development of osteonecrosis of the femoral head. The incidence and risk factors for osteonecrosis of the femoral head were identified, comparing various parameters concerning bone marrow transplantation between the groups with and without evidence of osteonecrosis. Nineteen (19%) of 100 patients had osteonecrosis of the femoral head develop. Four factors were found to be statistically significantly different between patients who had osteonecrosis develop and those who did not: younger age at the time of bone marrow transplantation, chronic graft-versus-host disease, cumulative dose of steroid, and intravenous pulse therapy with methylprednisolone. It was concluded that a low rate of complications and low dose steroid administration would reduce the incidence of osteonecrosis after bone marrow transplantation.

Reconstruction of the primate mandible with a combination graft of recombinant human bone morphogenetic protein-2 and bone marrow.

PURPOSE: This study evaluated whether recombinant human bone morphogenetic protein-2 (rhBMP-2) can be used to regenerate a resected part of the mandible in a primate model. MATERIALS AND METHODS: Segmental bone defects were created surgically in the mandible of Japanese monkeys. rhBMP-2 was suspended in a solution of polyglycolic co-lactic acid (PGLA) and lyophilized to make a BMP/PGLA complex. The rhBMP-2/PGLA complex and autogenous bone marrow in ratios of 3:0, 2.5:0.5, or 2:1 (vol:vol) were each implanted into the bone defects in 3 monkeys. Bone marrow or P(GLA alone were each implanted in 1 monkey as a control. The animals were killed 16 weeks after surgery, followed by radiologic and histologic evaluation. RESULTS: The implantation of bone marrow alone succeeded in reconstruction of the mandible, but the implantation of the rhBMP-2/PGLA complex showed only a small amount of bone formation. The combination graft of rhBMP-2/PGLA and bone marrow resulted in a greater degree of bone formation; especially the 2:1 combination showed the same result as only bone marrow implantation. CONCLUSION: The combination graft of rhBMP-2 and bone marrow, which requires only a small amount of bone marrow, was a reliable method for reconstruction of mandibular segmental defects in this animal model.

Radiologic findings: pulmonary infections after bone marrow transplantation.

Pulmonary infections are a significant source of morbidity and mortality in the bone marrow transplant population. This pictorial essay reviews the typical time period and imaging findings associated with common pulmonary pathogens that affect bone marrow transplant recipients.

MR imaging of multiple myeloma patients with bone-marrow transplants.

PURPOSE: To evaluate the role of MR imaging in the examination of multiple myeloma (MM) patients with bone-marrow transplants. MATERIAL AND METHODS: A total of 40 MR examinations were made of 20 patients: 33 examinations of the spine and pelvis in 20/20 patients; and 7 examinations of the femora in 5/20 patients. The 40 examinations were evaluated and the results compared with those found at radiography. Altogether 13/20 patients were re-examined: 10 after 1 year (1 patient twice); and 3 after 2 years. Five sequences were tested, 3 of them first without and then with i.v. contrast enhancement. RESULTS: In 24/33 examinations, active MM lesions were shown by MR. In 16/33 examinations, MR showed greater spread and detectability than radiography. In the 5/20 femoral patients, 3 had a peripheral red bone-marrow extension in the femora. In the 13 re-examinations, the lesions had spread in 4 patients, were unchanged in 7, and had decreased in 2. The lesions were easier to detect with the turbo inversion recovery (TIR) technique and with fat saturation than with the conventional spin-echo sequences. Contrast enhancement made the lesions more conspicuous in 8/17 examinations. CONCLUSION: MR has the potential to be a useful routine examination with T1-weighted and TIR sequences of selected areas, and without the use of contrast enhancement. However, further longitudinal studies are necessary in order to evaluate its possible predictive value.

Intraosseous compared to intravenous infusion of allogeneic bone marrow.

Thirty-eight patients (> or = 18 years) receiving marrow transplants from HLA-identical or one antigen-mismatched related donors were randomized to intraosseous (i.o.) + intravenous (i.v.) (n = 10), i.o. (n = 8) or i.v. (n = 20) infusions of bone marrow. There were no significant differences in patient characteristics. PMN/l more than 0.5 x 10(9) occurred on days 19 (median), 20 and 18.5 in the i.o. + i.v., i.o. and i.v. groups, respectively. We found a significant reduction in the number of days on total parenteral nutrition (P = 0.03) and a tendency to a reduction in the number of days on antibiotics (P = 0.06) in the i.o. compared to the i.v. group. Bacteraemia did not occur in the i.o. group, but was seen in 30% of the i.v. group (NS). The incidences of acute and chronic graft-versus-host disease, transplantation-related mortality, relapse and patient survival rates were similar in the three groups. Five patients examined with bone marrow scintigraphy showed the same distribution of granulocytes in the bone marrow directly after transplantation and 3 weeks after transplantation, whether the bone marrow was given by the i.o. or by the i.v. route. We conclude that allogeneic bone marrow transplantation can safely be performed by i.o. infusion, but haematopoietic recovery is not improved.

Dynamic scintigraphy of bone and bone marrow in multiple myeloma patients with bone-marrow transplants.

PURPOSE: To determine whether dynamic registration at bone and bone-marrow scintigraphy produces additional information compared to subsequent static registrations of bone-marrow transplants in multiple myeloma patients. MATERIAL AND METHODS: In a prospective study, 8 dynamic bone and 6 dynamic bone-marrow scintigraphies were performed in 10 patients. The dynamic scintigraphies were compared with conventional radiography, MR images, and static scintigraphies of bone and bone marrow. RESULTS: No additional information was revealed by the dynamic registration method; on the contrary, 4 of the 8 known lesions were not discerned at dynamic registration. An incidental observation was that the time-activity curves of both radiopharmaceuticals had a specific pattern. CONCLUSION: Dynamic registration at bone and bone-marrow scintigraphy was not useful for detecting disease in multiple myeloma lesions.